Publications of Tarnoki, A. D.
Heritability of the dimensions, compliance and distensibility of the human internal jugular vein wall
Aims The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. Methods 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. Results Genetic factors are responsible for 30–70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). Conclusions Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans.
Positive association and future perspectives of mitochondrial DNA copy number and telomere length – a pilot twin study. Archives of Medical Science. 2019.
Positive association and future perspectives of mitochondrial DNA copy number and telomere length – a pilot twin study
Introduction Recent experimental and population studies have highlighted the existence of telomere-mitochondria interplay. Besides studies revealing the molecular mechanisms underlying the associations of telomere defects and mitochondrial functions, investigations of mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in healthy and disease phenotypes have likewise begun, with the aim of gaining more insights about their relationship in humans. Material and methods A total of 142 asymptomatic adult twins, comprising 96 monozygotic (MZ) and 46 dizygotic (DZ) twins (mean age: 50.54 ±15.43 years), members of the Hungarian Twin Registry, were included in the analysis. Applying the qPCR standard curve method, we investigated the relationship of mtDNA copy number, telomere length and clinical data, besides assessing co-twin similarities of MZ and DZ twins for their mtDNAcn and TL measures. Results We found that twins were similar in their intraclass correlation coefficients irrespective of zygosity, suggesting a possibly more important role of common (shared) environmental factors compared to non-shared (unique) environmental and to a smaller degree also individual genetic influences. We confirmed a significant positive association between mtDNAcn and TL (r = 0.28, p < 0.01) in age- and sex-corrected analysis. Following bivariate estimates and correction with significant predictors, the independent positive associations were further verified. Conclusions Our results extend the until now modest number of studies investigating mtDNAcn and TL simultaneously in humans. In addition, we are the first to examine the relationship between mtDNAcn and telomere length in MZ and DZ twin subjects.
The Hungarian Twin Registry Update: Turning From a Voluntary to a Population-Based Registry. Twin Research and Human Genetic. 2019;22:561-6.
The Hungarian Twin Registry Update: Turning From a Voluntary to a Population-Based Registry
Since our last report on the voluntary Hungarian Twin Registry (HTR) in 2012, the number of pairs or multiplets included increased from 310 to 1044. Efforts to turn the registry into a population-based one are on the way. Nearly 128,000 twins living in Hungary (98,500 adults) will be mailed information on how to register on the new HTR website. Twins will be asked to invite their spouses and immediate family members. Meanwhile, strong cooperation through exchange programs has been developed with other foreign twin registries. Current research focuses on radiogenomics, musculoskeletal, cardiovascular and respiratory diseases, gut microbiome as well as basic molecular research and yielded new awards and further publications.
Are the Variants of the Circle of Willis Determined by Genetic or Environmental Factors? Results of a Twin Study Running title: Circle of Willis Variants in Twins
Background: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. Methods: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. Results: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. Conclusion: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.
Genetic and environmental determinants of longitudinal stability of arterial stiffness and wave reflection. A twin study. Journal of Hypertension. 2018;36(12):2316-23.
Genetic and environmental determinants of longitudinal stability of arterial stiffness and wave reflection. A twin study
Background: We aimed at evaluating the impact of genetic and environmental factors on longitudinal changes in aortic pulse wave velocity (aPWV) and aortic augmentation index (aAIx). Method: Three hundred and sixty-eight Italian and Hungarian adult twins (214 monozygotic, 154 dizygotic) underwent repeated evaluations of aPWV and aAIx (TensioMed Arteriograph). Within-individual/cross-wave, cross-twin/within-wave and cross-twin/cross-wave correlations were calculated; bivariate Cholesky models were fitted to calculate additive genetic (A), shared environmental (C) and unique environmental (E) components. Results: For both aPWV and aAIx, cross-twin correlations in monozygotic pairs (r between 0.35 and 0.56) were all significant and always higher than in dizygotic pairs, both at wave 1 and at wave 2. Heritability and unshared environmental proportion of variance at each wave were substantially time-invariant for aPWV (heritability 0.51, 95% CI 0.36–0.63 at wave 1; 0.49, 95% CI 0.34–0.62 at wave 2), whereas for aAIx, we observed a diminished genetic effect (heritability 0.57, 95% CI 0.45–0.67 at wave 1; 0.37, 95% CI 0.21–0.51 at wave 2). Overlapping genetic factors explained a high proportion (0.88, 95% CI 0.61–1.00) of longitudinal covariance for aPWV, and had a relatively lower impact on aAIx (0.55, 95% CI 0.35–0.70). Genetic correlations of aPWV (r = 0.64, 95% CI 0.42–0.85) and aAIx (r = 0.70, 95% CI 0.52–0.87) between waves were lower than 1, suggesting a potential contribution of novel genetic variance on arterial stiffening. Conclusion: Changes in aPWV and aAIx over time are largely genetically determined. Our results might stimulate further studies on genetic and epigenetic factors influencing the process of vascular ageing.
Genetically determined pattern of left ventricular function in normal and hypertensive hearts. Journal of Clinical Hypertension. 2018;20(5).
Genetically determined pattern of left ventricular function in normal and hypertensive hearts
We sought to assess the inheritance of left ventricular (LV) function using speckle‐tracking echocardiography and the impact of hypertension on modifying the genetically determined pattern of contraction in a population of twins. We recruited 92 Caucasian twin pairs, including 74 hypertensive (HTN) siblings. Beyond standard echocardiographic protocol, a speckle‐tracking analysis was performed, including global longitudinal strain (GLS). Systolic function, as assessed by ejection fraction, showed moderate heritability (61%); however, GLS showed higher and dominant heritability (75%). Heterogeneity models revealed that there were no differences between the HTN and non‐HTN subjects regarding the heritability of GLS. However, the heritability estimates of diastolic function parameters, including early diastolic strain rate, were low. LV systolic biomechanics is highly heritable. GLS shows dominant heritability, despite the presence of early‐stage hypertensive heart disease. Early diastolic parameters are rather determined by environmental factors. These findings suggest the presence of a genetic framework that conserves systolic function despite the expression of diastolic dysfunction and may underlie the phenotypic progression towards heart failure with preserved ejection fraction.
Investigation of circle of Willis variants and hemodynamic parameters in twins using transcranial color-coded Doppler sonography. The International Journal of Cardiovascular Imaging. 2018;34(9):14919-1427.
Investigation of circle of Willis variants and hemodynamic parameters in twins using transcranial color-coded Doppler sonography
Morphological and hemodynamic variations of the circle of Willis (CW) may have an important impact on cerebrovascular events. However, the environmental and genetic influence remains unclear. For this reason we studied the variations and hemodynamic parameters of the CW in twins using transcranial color-coded sonography (TCCS). Sixty-four twins, 19 monozygotic (MZ) and 13 dizygotic (DZ) pairs from the Italian Twin Registry (average age 45.0 ± 13.7 years) underwent TCCS and risk factor assessment. We examined CW morphology and recorded peak systolic velocity (PSV), end-diastolic velocity (EDV) and pulsatility index (PI). Raw heritability was determined for hemodynamic parameters, whereas concordance and discordance rates were calculated for CW morphological variants. A normal CW anatomy was observed in the majority of MZ and DZ twins (76.5% and 92.3%, respectively). The most frequent variant was a missing anterior cerebral artery (ACA). There was no significant difference in the prevalence of most CW variants depending on the zigosity. Concordance rates were low regarding the presence of variant CW anatomy both in MZ and DZ groups (0.14 and 0.00, respectively). Women had a significantly higher PI in vertebral arteries (VA) and in the right ACA (p = 0.01, p = 0.02 and p < 0.01, respectively). An inverse correlation was observed between hemodynamic parameters and age. Morphological variants of the CW do not seem to be heritable; they are most likely determined by environmental factors. In contrast, hemodynamic parameters of the CW are moderately heritable and this might have implications in the management and prevention of cerebrovascular diseases.
Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity. Cellular and Molecular Life Sciences. 2018;75(13):2447-56.
Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity
Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals. Twin data of telomerase activity (TA), hTERT protein level, telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were analyzed for co-twin similarity. The present study has provided novel information by demonstrating very high intraclass correlation (ICC) of hTERT protein level in T lymphocytes (0.891) and in both Th (0.896), Treg (0.885) and Tc (0.798) cell subgroups. When comparing results measured from PBMCs, intraclass correlation was also high for telomere length (0.815) and considerable for mtDNA copy number (0.524), and again exceptionally high for the rate-limiting telomerase subunit, hTERT protein level (0.946). In contrast, telomerase activity showed no co-twin similarity (ICC 0). By comparing relative amounts of hTERT protein levels in different lymphocyte subgroups of twin subjects, in Treg cells significantly higher level could be detected compared to Tly, Th or Tc cell subgroups. This is the first study that simultaneously analyzed co-twin similarity in MZ twins for the above four variables and alongside assessed their relationship, whereby positive association was found between TL and mtDNAcn.
Genetic and Environmental Effects on Eudaimonic and Hedonic Well-Being: Evidence from a Post-Communist Culture. Current Psychology. 2017;36:84-9.
Genetic and Environmental Effects on Eudaimonic and Hedonic Well-Being: Evidence from a Post-Communist Culture
Prior behavioral genetic studies in positive psychology were entirely based on data from Western democracies, leaving the question open whether the magnitude of genetic effects on well-being indicators is similar in substantially different societal contexts. The aim of this study, therefore, was to investigate the structure of the genetic and environmental influences on happiness, life satisfaction, meaning in life, optimism, sense of coherence, and general well-being in a non-Western sample. Altogether, 100 monozygotic and 36 same-sex dizygotic twin pairs from Hungary (73 % female; Mage = 43 years, SD = 16 years) participated in the survey. Univariate classical twin modeling (ACE analysis) was performed using structural equation models. Heritability estimates of the positive psychological variables were largely variable, ranging from 0 % (happiness and meaning in life) to 67 % (life satisfaction). Also, estimates for the influence of common environment fell between 0 % (life satisfaction, sense of coherence, and well-being) and 60 % (meaning in life). Unshared environmental influences however, explained a moderate variance of all investigated variables (33–62 %). Most results were in line with previous findings from Western countries; however, some notable differences—e.g., lower hereditary influence for happiness or more robust role of shared environmental effects for optimism—were also established. These findings suggest that the communist and post-communist legacy did not produce drastic differences in the structure of heritability and environmental influences as compared to countries with longer traditions of democracy and economic prosperity.
Van-e összefüggés az epikardiális zsírszövet és a koszorúér-betegség között? Cardiologia Hungarica. 2017;47(1):25-9.
Van-e összefüggés az epikardiális zsírszövet és a koszorúér-betegség között?
A zsírszöveti kompartmenteknek szerepe lehet az ateroszklerózis kialakulásában. Korábbi adatok az abdominalis zsírszövet és a fokozott kardiovaszkuláris kockázat közötti összefüggést már igazolták, napjainkban vizsgálat tárgyát képezi az epikardiális zsírszövet (EAT) szerepe is. Egyre több adat utal arra, hogy az EAT megnövekedett mennyisége a koronáriabetegség (CAD) kockázatát növeli. Jelenlegi vizsgálatunk során arra kerestünk választ, hogy igazolható-e összefüggés az EAT térfogata és a CAD jelenléte között felnőtt, korábban kardiális eseményt nem szenvedett egyének körében. A vizsgálatot a BUDAPEST-GLOBAL-tanulmány keretei között végeztük. Összesen 195 beteg (életkor: 56,1±9,4 év; nők 64,1%) adatait elemeztük. Minden résztvevőről kontrasztanyag nélküli CT-felvétel készült a mellkasi és felhasi régióban az EAT és az abdominalis zsírszövet mennyiségének méréséhez. A CAD jelenlétét vagy hiányát koronária-CT-angiográfi a lelete alapján állapítottuk meg és a betegeket koronáriabetegségben nem szenvedők (CAD-negatív; n=89) és koronáriabetegségben szenvedők (CAD-pozitív; n=106) csoportba soroltuk. A CAD-pozitív csoport életkora, haskörfogata, EAT- és abdominalis zsírszövetértéke számottevően nagyobb volt, mint a CAD-negatív csoporté. A CAD-pozitív csoportban értékelhetően kisebb arányban voltak a nők, az előzményi adatok között gyakrabban szerepelt hipertónia, dyslipidaemia és diabétesz. A CAD-pozitív csoport szérum trigliceridértéke értékelhetően nagyobb volt, mint a CAD-negatív csoporté, a többi lipid- és vércukorértéket tekintve a két csoport között számottevő különbség nem mutatkozott. Az életkor (esélyhányados: 1,1; p<0,001), a hipertónia (esélyhányados 3,3; p<0,05), a női nem (esélyhányados 0,1; p<0,001) és az EAT 10 cm3-nyi értéke (esélyhányados 1,3; p=0,001) a CAD független prediktorainak bizonyult. Az EAT mennyiségének 10 cm3-rel való növekedése a CAD kockázatát 30%-kal megnövelte. A női nem protektív tényezőnek adódott, következésképpen a férfi nem pozitív prediktív tényezőnek minősült. Az EAT mennyisége összefüggésben áll a CAD jelenlétével, ezért érdemes megfontolni értékének szerepeltetését a kardiovaszkuláris kockázatbecslő rendszerekben, a pontosság növelése érdekében. Is there any association between epicardial adipose tissue compartment and coronary artery disease? Various fat compartments might have an important role in the pathophysiology of atherosclerosis. Previous studies demonstrated an association between abdominal adipose tissue compartments and increased cardiovascular risk however the role of epicardial adipose tissue (EAT) is still unclear. It has been suggested that increased EAT quantity increases the risk of coronary artery disease (CAD). Our aim was to assess the relationship between the volume of EAT and the presence of CAD in subjects with negative cardiovascular medical history. We included 195 subjects (age: 56.1±9.4 years, female 64.1%) from the BUDAPEST-GLOBAL study. All subjects underwent coronary CT angiography (CTA) and were classifi ed into groups with and without CAD (CAD-positive: n=106 and CAD-negative: n=89, respectively), based on the presence or absence of any plaque in coronary CTA. We measured the EAT volume on a native cardiac scan and the abdominal adipose tissue areas on a single CT-slice acquired at the L3/L4 level. Subjects from the CAD-positive group were older, had a larger waist circumference, EAT volume and abdominal adipose tissue areas than subjects from the CAD-negative group. There were fewer females in the CAD-positive group, and in this group the presence of hypertension, dyslipidemia and diabetes were more frequent. Considering the lipid and glucose levels, we observed a signifi cant difference only in the serum triglyceride levels. Age (OR: 1.1 p<0.001), hypertension (OR: 3.3 p<0.05), female sex (OR: 0.1 p<0.001) and the volume of EAT in 10 cm3 clusters (OR: 1.3 p=0.001) were independent predictors for CAD. A 10 cm3 increment in the volume of EAT increases the risk of CAD with 30%. Female sex was a protective factor therefore male sex is a positive predictive factor. Since EAT shows a signifi cant association with the presence of CAD, it is reasonable to consider the quantity of EAT in risk assessments to improve the accuracy of CAD risk prediction.
Heritability of the femoral intima media thickness. European Journal of Internal Medicine. 2017;41:44-8.
Heritability of the femoral intima media thickness
Background The measurement of femoral intima-media thickness (IMT) is underutilized in the clinical practice, although it is a surrogate marker of cardiovascular disease. Materials and methods 388 Hungarian and Italian twins (121 monozygotic, 73 dizygotic pairs) underwent bilateral B-mode sonography of femoral arteries. IMT was measured by semiautomated software, where available, or by calipers. Results Within-pair correlation in monozygotic twins was higher than in dizygotics for each parameter. Age-, sex- and country-adjusted genetic effect accounted for 43.9% (95% confidence interval, CI 21.3%–65.2%) and 47.2% (95% CI, 31.4%–62.6%) of the variance of common and superficial femoral artery IMT, respectively, and unshared environmental effect for 56.1% (95% CI 34.6%–78.5%) and 52.8% (95% CI, 37.2%–68.5%). These results did not change significantly after correcting for body mass index or central systolic blood pressure. Conclusions Genetic factors have a moderate role in the determination of common and superficial femoral IMT; however, the influence of environmental (lifestyle) factors remains still relevant. Environmental factors may have a role in influencing the genetic predisposition for femoral vascular hypertrophy.
Vertebral artery diameter and flow: nature or nurture. Neuroimaging. 2017;27(5).
Vertebral artery diameter and flow: nature or nurture
BACKGROUND AND PURPOSE In contrast with the carotid arteries, the vertebral arteries (VAs) show considerable variation in length, caliber, and vessel course. This study investigated whether the variation in diameter and flow characteristics of the VAs might be inherited. METHODS A total of 172 Italian twins from Padua, Perugia, and Terni (54 monozygotic, 32 dizygotic) recruited from the Italian Twin Registry underwent B‐mode and pulsed‐wave Doppler ultrasound assessment of their VAs. VA diameters, peak systolic velocity (PSV) and end diastolic velocity (EDV) were assessed at the level of a horizontal V2 segment. Univariate quantitative genetic modeling was performed. RESULTS Fourteen percent of the sample had VA hypoplasia. Within pair correlation in monozygotic twins was higher than in dizygotics (.552 vs. .229) for VA diameter. Age‐ and sex‐adjusted genetic effect, under the most parsimonious model, accounted for 54.7% (95% CI: 42.2‐69.1%) of the variance of VA diameter, and unshared environmental effect for 45.3% (95% CI: 30.9‐57.8%). No heritability was found for the PSV of VA, but shared (34.1%; 95% CI: 16.7‐53.7%) and unshared (65.9%; 95% CI: 45.9‐83.1%) environmental factors determined the variance. EDV of VA is moderately genetically influenced (42.4%; 95% CI: 16.1‐64.9%) and also determined by the unshared environment (57.6%; 95% CI: 34.7‐83.7%). CONCLUSIONS The diameter of the VAs is moderately genetically determined. Different factors influence the PSV and EDV of VAs, which may highlight the complex hemodynamic background of VA flow and help to understand the vertebral flow anomalies found by ultrasound.
The inheritance of corneal endothelial cell density. Ophthalmic Genetics. 2016;37(3).
The inheritance of corneal endothelial cell density
Background: Although it is known that some corneal diseases and degenerations have a significant heritable background, heritability on corneal endothelial cell density (ECD) has never been clearly determined. Our aim was to determine the heritability of corneal ECD. Material and methods: Corneal ECD of 114 eyes (66 eyes of 33 monozygotic and 48 eyes of 24 dizygotic pairs; mean age 49.0 ± 15.5 years) was investigated by Konan Noncon Robo NSP-9900 specular microscopy. Structural equation modeling (ACE model) was applied. Results: Endothelial corneal cell density was highly heritable (82.0%, 95%CI, 70.0–92.0%), whereas the unique environmental contribution was 18.0% (95%CI, 8.0–29.0%). Shared environmental factors had no influence on the endothelial corneal cell density. Discussion: In this twin study, we established first that the density of the corneal endothelial cells is strongly heritable, which should stimulate future genetic studies to identify genes and pathways that are involved in determining ECD which might in turn lead to future treatments to prevent EC loss.
Az alvás alatti légzészavarok hátterében álló örökletes tényezők: egy ikervizsgálat tapasztalatai. Medicina Thoracalis. 2016;69(2):87-95.
Az alvás alatti légzészavarok hátterében álló örökletes tényezők: egy ikervizsgálat tapasztalatai
Bár az obstruktív alvási apnoe (OSA) gyakran előforduló betegség, a kialakulásukban szerepet játszó örökletes tényezők szerepe mindmáig ismeretlen. A Magyar Ikerregiszter 110 ikertagja (39 egypetéjű, monozigóta, MZ, és 16 kétpetéjű, dizigóta, DZ ikerpár; átlag életkor 50+-16 év) éjjeli poliszomnográfiás vizsgálaton esett át. Regisztráltuk az apnoe hypopnoe indexet (AHI), a légzészavar indexet (respiratory disturbance index, RDI) és az oxigén deszaturációs indexet (ODI). Az ikerpárok közötti korrelációkat összehasonlítva kiszámítottuk a nyers öröklődési mutatókat (Falconer-formula). OSA 23 vizsgált személynél fordult elő (21%). Mindhárom mért paraméter esetén a korrelációs együtthatók magasabbak voltak az egypetéjű iker-pároknál (0,80 vs. 0,15, 0,70 vs. 0,12 és 0,80 vs. 0,42, MZ vs. DZ, AHI, RDI és ODI esetén), amik magas (1,30, 1,17 és 0,76) nyers örökletességi mutatót jelentenek. Gyenge összefüggés igazolódott az alvászavarral összefüggő változók és a testsúly-testmagasság index (BMI, p<0,005, R2=0,078-0,224), illetve a reggeli systolés és diastolés vérnyomásértékek (SBP, DBP) között (p<0,05, R2=0,043-0,093, kivéve az RDI-t, ahol p=ns). Ezek nyers örökletességi indexe magasnak (BMI: h2=1,730, reggeli SBP és DBP: h2=0,568, h2=0,422) bizonyult. Vizsgálatunkban elsőként mutattuk ki az alvásfüggő légzészavar paramétereinek örökletességét, mely felveti az OSA kialakulásáért felelős genetikai faktorok szerepét. Ezt részben a BMI magas örökletessége magyarázhatja. A vizsgálat folytatása szükséges nagyobb ikermintán, hogy megállapíthassuk a közös és egyéni környezeti tényezők pontos szerepének mértékét. További kutatások feladata feltárni, hogy érdemes-e szűrni az OSA-s betegek közeli rokonait. A kutatást a Magyar Pulmonológiai Alapítvány támogatta (MPA, 2013).
Genetic and Environmental Effects on the Abdominal Aortic Diameter Development. Arquivos Brasileiros de Cardiologia. 2016.
Genetic and Environmental Effects on the Abdominal Aortic Diameter Development
Background Configuration of the abdominal aorta is related to healthy aging and a variety of disorders. Objectives We aimed to assess heritable and environmental effects on the abdominal aortic diameter. Methods 114 adult (69 monozygotic, 45 same-sex dizygotic) twin pairs (mean age 43.6 ± 16.3 years) underwent abdominal ultrasound with Esaote MyLab 70X ultrasound machine to visualize the abdominal aorta below the level of the origin of the renal arteries and 1-3 cm above the bifurcation. Results Age- and sex-adjusted heritability of the abdominal aortic diameter below the level of the origin of the renal arteries was 40% [95% confidence interval (CI), 14 to 67%] and 55% above the aortic bifurcation (95% CI, 45 to 70%). None of the aortic diameters showed common environmental effects, but unshared environmental effects were responsible for 60% and 45% of the traits, respectively. Conclusions Our analysis documents the moderate heritability and its segment-specific difference of the abdominal aortic diameter. The moderate part of variance was explained by unshared environmental components, emphasizing the importance of lifestyle factors in primary prevention. Further studies in this field may guide future gene-mapping efforts and investigate specific lifestyle factors to prevent abdominal aortic dilatation and its complications.
Environmental Factors Account for Variability of Hepatic Vein Flow: a Doppler assessment in healthy twins. The Chinese Journal of Physiology. 2016;59(1):33-8.
Environmental Factors Account for Variability of Hepatic Vein Flow: a Doppler assessment in healthy twins
Doppler interrogation studies of the liver blood flow indicate altered hepatic vein waveforms in association with impaired hepatocellular function. However, little is known about the mechanisms responsible for variations of these parameters in the absence of disease. We aimed to investigate the contribution of heritable and environmental factors to the physiological variability of hepatic vein flow in a twin cohort. Two hundred twenty-eight healthy adult Hungarian twins (69 monozygotic, 45 same-sex dizygotic pairs) underwent Doppler sonography of the hepatic vein. Age- and sex-adjusted heritability of the highest velocity (amplitude of S wave) of hepatic vein flow was negligible. Shared environment contributed to 33% (95% CI, 16%-51%), and unshared environment was responsible for the largest portion (67%; 95% CI, 49%-84%) of the variance. Duration of sports activities was significantly (P < 0.05) related to the magnitude of hepatic vein flow, while other risk factors and lifestyle characteristics had no significant influence. The data suggest that genetic factors have little impact on the parameters of hepatic venous blood flow. The variability observed in healthy twins by the Doppler interrogation can be explained by the effect of unshared environmental components primarily related to regular physical activity. These findings underscore the importance of unique environments in physiological variations of hepatic venous blood flow.
Rationale, design and methodological aspects of the BUDAPEST-GLOBAL study (Burden of Atherosclerotic Plaques Study in Twins - Genetic Loci and the Burden of Atherosclerotic Lesions)
The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST‐GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single‐center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same‐sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non–contrast‐enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non–contrast‐enhanced image slice was acquired at the level of L3‐L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3‐dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per‐patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST‐GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders.
Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study
OBJECTIVES: Decreased thyroid volume has been related to increased prevalence of thyroid cancer. SUBJECTS AND METHODS: One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63). RESULTS: Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%). CONCLUSIONS: Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects.
Different genetic impact in the development of renal length and width: a twin study. Internal Medicine Journal. 2015;45(1).
Different genetic impact in the development of renal length and width: a twin study
Background Ultrasound measurements of renal dimensions are conventionally limited to renal length, shape and cortical thickness. These are regarded as adequate for normal therapeutic decision‐making and volume measurements are reserved for a few clinical trials. However, there is no evidence concerning the degree to which renal length or volume is independently susceptible to heritable and environmental influences. Aim We aimed to determine whether renal length or width (as a surrogate of volume) was more influenced by heritability. Methods A single operator measured renal length and width in 114 adult monozygotic and same‐sex dizygotic Hungarian twin pairs (mean age 43.6 ± 16.3 years), using an Esaote MyLab 70X ultrasound machine with curved array transducer (1–8 MHz, CA431). Results Analysis of within‐pair co‐twin correlations adjusted for age and gender showed that the age‐ and sex‐adjusted heritability of average renal length was 51% (95% confidence interval, 29–72%). Renal width showed negligible genetic influence. Common environmental effects had no influence, and unshared environments were responsible for 49–80% of the variance, mainly renal width. Conclusions This study is the first to demonstrate the moderate heritability and limited environmental influence on renal length, and the contrasting lack of heritability of renal width, which is mainly influenced by unshared environmental components, that is lifestyle habits. Renal width therefore better represents the influence of modifiable environmental factors than renal length. The results suggest that renal width not length should be reported to facilitate early detection and monitoring of renal disease.
Heritability of cerebral arterial velocity and resistance. Journal of Cardiovascular Medicine. 2014;18(1):28-33.
Heritability of cerebral arterial velocity and resistance
Aims Cerebrovascular resistance is a pressure-dependent mechanism resulting from cerebral autoregulation, which is the normal buffering of changes in arterial blood pressure. Lifestyle habits are known to have an influence; however, its magnitude is still unclear. The aim of this study was to assess the contribution of additive genetic, shared and unshared environmental factors to changes in middle cerebral artery (MCA) mean flow velocities (MFVs) and pulsatility index. Methods One hundred and forty-three Italian twin pairs from Padua, Perugia and Rome (68 monozygotic, 75 dizygotic, 55 ± 12 years) underwent transcranial Doppler sonography of the MCA bilaterally. Univariate quantitative genetic modeling was performed to decompose the phenotypic variance of averaged MFV and pulsatility index into additive genetic, shared and unique environmental effects adjusted by age and sex. Results MFV was heritable in 30.6% [95% confidence interval (CI) 0.8–67.3%], and shared and unshared environmental factors explained 47.7 and 21.6% of the variance (95% CI 14.4–71.9% and 12.6–32.0%). Pulsatility index was not genetically determined, but unique and common environmental factors were responsible for 54.2 and 38.1% of the variance (95% CI 36.3–71.8% and 0.0–57.8%). Conclusion These findings underline the importance of identification of the specific genes and common environmental factors related to MFV. Individuals with positive family history of stroke related to the atherosclerosis of MCA might take advantage from preventive ultrasound screening. More emphasis should be placed on the prevention of the known related common environmental factors on MFV and the individual lifestyle risk factors on pulsatility index.
Genetic covariance between central corneal thickness and anterior chamber volume: a Hungarian twin study. Twin Research and Human Genetics. 2014;17(5).
Genetic covariance between central corneal thickness and anterior chamber volume: a Hungarian twin study
Background: Few, and inconsistent, studies have showed high heritability of some parameters of the anterior segment of the eye; however, no heritability of anterior chamber volume (ACV) has been reported, and no study has been performed to investigate the correlation between the ACV and central corneal thickness (CCT). Methods: Anterior segment measurements (Pentacam, Oculus) were obtained from 220 eyes of 110 adult Hungarian twins (41 monozygotic and 14 same-sex dizygotic pairs; 80% women; age 48.6 ± 15.5 years) obtained from the Hungarian Twin Registry. Results: Age- and sex-adjusted heritability of ACV was 85% (bootstrapped 95% confidence interval; CI: 69% to 93%), and 88% for CCT (CI: 79% to 95%). Common environmental effects had no influence, and unshared environmental factors were responsible for 12% and 15% of the variance, respectively. The correlation between ACV and CCT was negative and significant (rph = −0.35, p < .05), and genetic factors accounted for the covariance significantly (0.934; CI: 0.418, 1.061) based on the bivariate Cholesky decomposition model. Conclusion: These findings support the high heritability of ACV and central corneal thickness, and a strong genetic covariance between them, which underscores the importance of identification of the specific genetic factors and the family risk-based screening of disorders related to these variables, such as open-angle and also angle closure glaucoma and corneal endothelial alterations.
Genetic effects on refraction and correlation with hemodynamic variables: a twin study. Acta Physiologica Hungarica. 2014;101(3):309-20.
Genetic effects on refraction and correlation with hemodynamic variables: a twin study
Spherical equivalent (SE) has not been linked to increased cardiovascular morbidity. Methods: 132 Hungarian twins (age 43.3±16.9 years) underwent refraction measurements (Huvitz MRK-3100 Premium AutoRefractokeratometer) and oscillometry (TensioMed Arteriograph). Results: Heritability analysis indicated major role for genetic components in the presence of right and left SE (82.7%, 95%CI, 62.9 to 93.7%, and 89.3%, 95%CI, 72.8 to 96.6%), while unshared environmental effects accounted for 17% (95%CI, 6.3% to 37%), and 11% (95%CI, 3.4% to 26.7%) of variations adjusted for age and sex. Bilateral SE showed weak age-dependent correlations with augmentation index (AIx), aortic pulse wave velocity (r ranging between 0.218 and 0.389, all p < 0.01), aortic systolic blood pressure and pulse pressure (r between 0.188 and 0.289, p < 0.05). Conclusions: These findings support heritability of spherical equivalent, which does not coexist with altered hemodynamics (e.g. accelerated arterial aging). Accordingly, SE and the investigated hemodynamic parameters seem neither phenotypically nor genetically associated. Keywords: arterial stiffness, augmentation index, genetics, heritability, refraction
Lack of heritability of exhaled volatile compound pattern: an electronic nose twin study. Journal of Breath Research. 2014;8(1).
Lack of heritability of exhaled volatile compound pattern: an electronic nose twin study
Electronic noses can distinguish various disorders by analyzing exhaled volatile organic compound (VOC) pattern; however it is unclear how hereditary and environmental backgrounds affect the exhaled VOC pattern. A twin study enrolling monozygotic (MZ) and dizygotic (DZ) twins is an ideal tool to separate the influence of these factors on the exhaled breath pattern. Exhaled breath samples were collected in duplicates from 28 never smoking twin pairs (in total 112 samples) without lung diseases and processed with an electronic nose (Cyranose 320). Univariate quantitative hereditary modeling (ACE analysis) adjusted for age and gender was performed to decompose the phenotypic variance of the exhaled volatile compound pattern (assessing principal components (PCs) derived from electronic nose data) into hereditary (A), shared (C), and unshared (E) environmental effects. Exhaled VOC pattern showed good intra-subject reproducibility as assessed with the Bland-Altman plot. Significant correlations were found between exhaled VOC patterns of both MZ and DZ twins. The hereditary background did not influence the VOC pattern. The shared environmental effect on PC 1, 2 and 3 was estimated to be 93%, 94% and 54%, respectively. The unshared (unique) environmental influence explained a smaller variance (7%, 6% and 46%). For the first time using the twin design, we have shown that the environmental background largely affects the exhaled volatile compound pattern in never smoking volunteers without respiratory disorders. Further studies should identify these environmental factors and also assess their influence on exhaled breath patterns in patients with lung diseases.
Genetic impact dominates over environmental effects in development of carotid artery stiffness: a twin study. Hypertension Research. 2014;37:88-93.
Genetic impact dominates over environmental effects in development of carotid artery stiffness: a twin study
Arterial stiffness is an independent predictor of cardiovascular, cerebrovascular and all-cause mortality. Quantifying the genetic influence on the stiff arterial phenotype allows us to better predict the development of arterial stiffness. In this study, we aimed to determine the heritability of carotid artery stiffness in healthy twins. We studied 98 twin pairs of both sexes. We determined carotid artery stiffness locally using echo tracking and applanation tonometry. We estimated the heritability of stiffness parameters using structural equation modeling. The carotid distensibility coefficient showed the highest heritability (64%, 95% confidence interval 45–77%). The incremental elastic modulus, compliance and stiffness index β also showed substantial heritability (62%, 61% and 58%, respectively). The remaining 36–42% phenotypic variance was attributed to unshared environmental effects. Genetic influence appears to dominate over environmental factors in the development of carotid artery stiffness. Environmental factors may have an important role in favorably influencing the genetic predisposition for accelerated arterial stiffening.
The Hungarian Twin Registry. Twin Research and Human Genetics. 2013;16(1).
The Hungarian Twin Registry
The first Hungarian Twin Registry was established in Budapest in 1970 through the mandatory reporting of multiple-births. In the 1980s a second, volunteer adult registry was also founded. Unfortunately, both registries ceased to exist in the 1990s. Efforts started in 2006 to revive a Hungarian twin registry. The team spearheading this effort reports here on this progress. Currently, the voluntary Hungarian Twin Registry consists of 310 adult twin pairs and multiplets. Current research focuses on cardiovascular and respiratory health and yielded multiple awards and publications. Efforts are on the way to expand into social, psychological, and obesity studies.
Magyarországi ikerkutatások: négy évtized eredményei. Orvosi Hetilap. 2013;154(40).
Magyarországi ikerkutatások: négy évtized eredményei
Az ikervizsgálatok szerepet játszanak a fenotípusos változók kialakulásáért felelős genetikai és környezeti tényezők arányának, továbbá a genotípusok közötti genetikai kapcsoltság vizsgálatában. Magyarországon az ikerkutatások döntően az 1970-es években kezdődtek és alapjukat három ikernyilvántartás (köztük két iker-regiszter) biztosította. A vizsgálatok elsősorban a különböző veleszületett rendellenességekre, a fogamzásgátló tabletták és a folsav ikergyakoriságra való hatására, az ikrek pszichoszexuális viselkedésének megismerésére, az alkoholfogyasztási szokások örökletességének becslésére irányultak. Először mutatták ki a laktóz(mal)abszorpció monogénes mendeli öröklődését. 2007-ben alakult meg a Magyar Ikerregiszter, amelynek segítségével több ikervizsgálatra nyílt ismét lehetőség, például a metabolikus szindróma és az érelmeszesedés hátterének megértésére. Nemzetközi ikervizsgálat során többek között az artériás stiffness, a centrális vérnyomás, a carotis intima/media falvastagság, a vénás biomechanika, a testösszetétel, a légzésfunkció és a dohányzási szokások vizsgálatára is sor került. Először sikerült kimutatni a nem alkoholos zsírmáj örökletességének hiányát és a carotisplakkok kialakulásában az öröklődés szerepét. A dolgozat a Magyar Ikerregiszter jövőbeni terveiről is áttekintést nyújt. Orv. Hetil., 2013, 154, 1579–1586. | Twin studies play a role in examining the contribution of genetic variations and environmental factors responsible for the determination of phenotypic variables and of genetic linkage between genotypes. Hungarian twin studies, supported by three twin registries (among them two twin-database), date back to 1970s. Studies mainly focused on various congenital abnormalities, the effect of contraceptive pills and folic acid on the frequency of twin pregnancies, as well as psychosexual and alcohol consumptional behaviors. Monogenic Mendelian inheritance of lactose (mal)absorption was demonstrated for the first time. Hungarian Twin Registry was founded in 2007, which contributed to the current understanding on the background of several disorders, e.g. metabolic syndrome and atherosclerosis. As part of an international twin study, among others, arterial stiffness, central blood pressure, carotid intima/media thickness, venous biomechanics, body composition, lung function and smoking characteristics were also assessed. Absence of genetic background in non-alcoholic fatty liver disease and high inheritance of carotid plaque characteristics were demonstrated for the first time. The review also aims to summarize future plans of the Hungarian Twin Registry. Orv. Hetil., 2013, 154, 1579–1586.
Genetic and environmental variance of renal parenchymal thickness: a twin study. Croatian Medical Journal. 2013;54(6):550-4.
Genetic and environmental variance of renal parenchymal thickness: a twin study
Aim: To estimate heritability and environmental effects on renal parenchymal thickness. Methods: In this twin study, renal parenchymal thickness of 98 Hungarian healthy adult twin pairs (68 monozygotic, 30 dizygotic) without kidney disease was measured bilaterally using renal ultrasound with Esaote MyLab 70X ultrasound machine with low-frequency curved transducers (1-8 MHz). Results: In both monozygotic and dizygotic group there were more women (76.5%). Mean right and left renal parenchymal thickness was 1.32 ± 0.33 cm and 1.62 ± 0.31 cm, respectively. Age-and sex-adjusted heritability of renal parenchymal thickness was 0.0% (95% confidence interval, 0.0 to 50.2%), shared and unshared environmental factor was 30.2% (4.1 to 55.9%) and 69.8% (45.8 to 89.5%), respectively. Conclusion: This study shows a negligible role of heritability and an important role of environmental effects in developing renal parenchymal thickness, emphasizing the importance of lifestyle for primary prevention.
Heritability of Venous Biomechanics. Arteriosclerosis Thrombosis and Vascular Biology. 2013;33(1):152-7.
Heritability of Venous Biomechanics
Objective-Altered venous biomechanics may contribute to the pathogenesis of venous diseases, and their heritability is less known. Methods and Results-Seventy-eight monozygotic twin pairs (aged 42.4±16.8 years) and 24 same-sex dizygotic twin pairs (aged 50.5±16.1 years) were examined. Anteroposterior and mediolateral diameters of the common femoral vein were measured by ultrasonography. Measurements were made both in supine and in standing body positions, with or without controlled forced expiration (Valsalva test). High correlation of diameter, capacity, and distensibility values was found between twin pairs. The univariate heritability (A), shared (C), and unshared (E) environmental effects model has shown 39.3% genetic component of the variance of low pressure, 37.9% of high-pressure venous capacity, and 36.4% of maximal capacity changes, even after elimination of sex, age, and body weight effects. Bivariate Cholesky analysis revealed substantial covariance of inherited body weight and venous capacity components (57.0%-81.4%). Conclusion-Femoral vein capacity and elasticity depend 30% to 40% on genetic factors, and this value in the standing body position can reach 50%. A relatively high genetic covariance was found between weight and femoral vein capacity and elasticity. Our work might yield some new insights into the inheritance of venous diseases that are associated with altered venous biomechanics and help elucidate the involved genes.
Association of body mass index with arterial stiffness and blood pressure components: a twin study. Atherosclerosis. 2013;229(2):388-95.
Association of body mass index with arterial stiffness and blood pressure components: a twin study
Rationale Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. Methods We studied 228 monozygotic and 150 dizygotic twin pairs aged 18–82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m2). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. Results Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%–58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = −0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%–77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15–0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). Conclusion Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important.
Genetic and environmental factors on the relation of lung function and arterial stiffness. Respiratory Medicine. 2013;107(6):927-35.
Genetic and environmental factors on the relation of lung function and arterial stiffness
Background An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. Methods 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV1/; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. Results Age-, sex-, country- and smoking-adjusted heritability of FEV1, percent predicted FEV1, FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45–85%), 28% (95% CI: 0–67%), 68% (95% CI: 20–81%) and 45% (95% CI: 0–66%), respectively. Measured and percent predicted FVC and FEV1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV1, FVC with brachial or aortic augmentation indices which ranged between −0.12 and −0.17. No genetic covariance between lung function and arterial stiffness was found. Conclusions Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.
Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection. Journal of Breath Research. 2013;7(2).
Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection
Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FENO) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FENO levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FENO was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aixao) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FENO and Aixao were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FENO with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FENO and Aixao (r = -0.17; 95%CI:-0.32,-0.02). FENO showed a significant negative genetic correlation with Aixao (rg = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FENO are explained both by genetic and non-shared environmental effects. Covariance between FENO and Aixao is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.
Evidence for a strong genetic influence on carotid plaque characteristics: an international twin study
Background and Purpose— Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. Methods— One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. Results— Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%–90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%–87%), 69% for plaque size (area in mm2 in longitudinal plane; < or >50 percentile; 95% CI, 16%–86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%–90%), 74% for plaque numerosity (95% CI, 26%–86%), 68% (95% CI, 40%–84%), and 66% (95% CI, 32%–90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%–34%). Controlling for relevant covariates did not change the results significantly. Conclusions— The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits.
Heritability of central blood pressure and arterial stiffness: a twin study. Journal of Hypertension. 2012;30(8):1564-71.
Heritability of central blood pressure and arterial stiffness: a twin study
OBJECTIVE: Central blood pressure and aortic stiffness have been consistently reported as strong cardiovascular risk factors. Twin studies by comparing identical with nonidentical twins produce information on the relative contribution of genes and environment. METHODS: One hundred and fifty-four monozygotic (MZ) and 42 dizygotic (DZ) twin pairs (age 43 ± 17 years) from Hungary and the United States underwent brachial and central augmentation index (AIx), brachial and central pressure, and aortic pulse wave velocity (PWV) measurements with the invasively validated Arteriograph device. Bivariate Cholesky decomposition models were applied. RESULTS: Age-adjusted, sex-adjusted and country-adjusted heritability was 60.0% for central SBP [95% confidence interval (CI), 44.8-69.6%], 50.1% for aortic PWV (95%CI, 26.0-66.8%), 48.7% for aortic AIx (95%CI, 1.7-74.0%), 46.8% for brachial AIx (95%CI, 1.1-73.8%), 46.7% for central pulse pressure (PP) (95%CI, 12.4-61.4%), and 30.0% for brachial PP (95%CI, 0.0-53.4%). Central SBP and PP had strong bivariate correlations with brachial (r = 0.461 and 0.425) and central AIx (r = 0.457 and 0.419), as well as with aortic PWV (r = 0.341 and 0.292, all P < 0.001). Brachial PP had a weak correlation with brachial AIx (r = -0.118, P < 0.05), central AIx (r = -0.122, P < 0.05), and none with aortic PWV (r = 0.08, P = n.s.). Genetic factors explained a moderate phenotypic correlation between central PP, SBP, brachial SBP and aortic PWV. CONCLUSIONS: Central systolic and PPs, brachial PP, AIx, aortic PWV are moderately heritable. A moderate genetic covariance among aortic PWV and central PP, central SBP and brachial SBP was found.
Heritability of non-alcoholic fatty liver disease and association with abnormal vascular parameters: A twin study. Liver International. 2012;32(8).
Heritability of non-alcoholic fatty liver disease and association with abnormal vascular parameters: A twin study
Background Non‐alcoholic fatty liver disease (NAFLD) has been linked to increased cardiovascular morbidity. However, genetic factors have an unclear role in this condition. Aims To analyse heritability of NAFLD and its association with abnormal vascular parameters in a large twin cohort. Methods Anthropometric and lipid metabolic parameters were obtained from 208 adult Hungarian twins (63 monozygotic and 41 dizygotic pairs; 58 men and 150 women; age 43.7 ± 16.7 years). B‐mode ultrasonography was performed to detect steatosis and categorize severity. Brachial and aortic augmentation indices and aortic pulse wave velocity were assessed using oscillometry (TensioMed Arteriograph). Carotid intima media thickness (IMT) was measured using ultrasonography on the proximal common, distal common and internal carotid arteries. Results NAFLD was identified in 47 subjects (22.6%), of which 44 (93.6%) had mild and 3 (6.4%) had moderate steatosis. These subjects were older (age: 50.9 ± 14.3 vs. 41.5 ± 16.7 years, P < 0.001) and had a higher body mass index (BMI; 30.1 ± 5.2 vs. 24.6 ± 4.1 km/m2, P < 0.001) than non‐NAFLD twins. Based on 91 same‐sex twin pairs, heritability analysis indicated no discernible role for genetic components in the presence of NAFLD (95% confidence interval, 0.0–36.0%), while shared and unshared environmental effects accounted for 74.2% and 25.8% of variations adjusted for age and BMI. Augmentation indices and carotid IMT in twins with NAFLD were increased at most examined locations (P < 0.05–P < 0.001). Conclusion These findings do not support heritability of NAFLD, although it coexists with vascular parameters linked to increased cardiovascular risk, underscoring the importance and value of prevention in this very common disorder.
Psychosexual Study of Communist Era Hungarian Twins. Twin Research and Human Genetics. 2011;14(2):144-9.
Psychosexual Study of Communist Era Hungarian Twins
Our aim in this study is to describe the characteristics of sexual development in twins and estimate the role of heritability and environmental factors as causes of certain sexual disorders. Two hundred and ten adult same-sex twin pairs (92 monozygotic [MZ] female, 41 MZ male, 55 dizygotic [DZ] female and 22 DZ male pairs) were involved in the study. Data were collected in 1982 by self-administered questionnaires that included items on sexual maturation, sexual life, contraception, mutual sexual activity within twin pairs and alcohol use. The ratio of married to unmarried twins was nearly the same in MZs and DZs, with the exception that the divorce rate was higher in MZ female twins (14%), and DZ and male twins were slightly more likely to be single. Menarche was later in twins compared to non-twin Hungarian women. 57% of MZs experienced menarche within 3 months of each other, 77% within 6 months while it occurred for 30% and 43% respectively in DZs. The first seminal emission indicated some delay in male twins compared with the Hungarian general population sample. MZ first kisses occurred later than DZ's first kisses. The same was true for the first petting, masturbation and first sexual intercourse. Anorgasmy is 27% heritable but the estimate is not statistically significant. Concordance rate for premature ejaculation in MZs was greater than in DZs but the structural equation model showed significant misfit. Age at menarche appeared to be strongly heritable.
Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study. Cardiovascular Diabetology. 2011;10(96).
Genetikai és környezeti tényezők szerepe a kardiometabolikus kockázati tényezők alakulásában: ikervizsgálatok eredményei. Metabolizmus. 2011;10(96):304-9.
A metabolikus szindróma összetevőinek genetikai meghatározottsága: ikervizsgálatok eredményei. Orvosi Hetilap . 2011;152(32):1265-71.
Effects of genetic versus environmental factors on cardiovascular autonomic function: a twin study. Diabetic Medicine. 2011;28(10):1241-8.
Twins lead to the prevention of atherosclerosis. Preliminary findings of International twin study. Journal for Vascular Ultrasound. 2011;35(2):61-71.