Genetic influences on the onset of obstructive sleep apnoea and daytime sleepiness: a twin study

Background Obstructive sleep apnoea (OSA) is one of the major sources of the excessive daily sleepiness, cognitive dysfunction, and it increases cardiovascular morbidity and mortality. Previous studies suggested a possible genetic influence, based on questionnaires but no objective genetic study was conducted to understand the exact variance underpinned by genetic factors. Methods Seventy-one Hungarian twin pairs involved from the Hungarian Twin Registry (48 monozygotic, MZ and 23 dizygotic, DZ pairs, mean age 51 ± 15 years) underwent overnight polysomnography (Somnoscreen Plus Tele PSG, Somnomedics GMBH, Germany). Apnoea hypopnea index (AHI), respiratory disturbance index (RDI) and oxygen desaturation index (ODI) were registered. Daytime sleepiness was measured with the Epworth Sleepiness Scale (ESS). Bivariate heritability analysis was applied. Results The prevalence of OSA was 41% in our study population. The heritability of the AHI, ODI and RDI ranged between 69% and 83%, while the OSA, defined by an AHI ≥5/h, was itself 73% heritable. The unshared environmental component explained the rest of the variance between 17% and 31%. Daytime sleepiness was mostly determined by the environment, and the variance was influenced in 34% by the additive genetic factors. These associations were present after additional adjustment for body mass index. Conclusion OSA and the indices of OSA severity are heritable, while daytime sleepiness is mostly influenced by environmental factors. Further studies should elucidate whether close relatives of patients with OSA may benefit from early family risk based screening.This study was supported by the Hungarian Pulmonology Foundation of the Hungarian Society of Pulmonologists (2014, TDL) and Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (AB)

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima–media thickness: A longitudinal twin study

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time

Association between birth weight and educational attainment : an individual-based pooled analysis of nine twin cohorts

Background There is evidence that birth weight is positively associated with education, but it remains unclear whether this association is explained by familial environmental factors, genetic factors or the intrauterine environment. We analysed the association between birth weight and educational years within twin pairs, which controls for genetic factors and the environment shared between co-twins. Methods The data were derived from nine twin cohorts in eight countries including 6116 complete twin pairs. The association between birth weight and educational attainment was analysed both between individuals and within pairs using linear regression analyses. Results In between-individual analyses, birth weight was not associated with educational years. Within-pairs analyses revealed positive but modest associations for some sex, zygosity and birth year groups. The greatest association was found in dizygotic (DZ) men (0.65 educational years/kg birth weight, p=0.006); smaller effects of 0.3 educational years/kg birth weight were found within monozygotic (MZ) twins of both sexes and opposite-sex DZ twins. The magnitude of the associations differed by birth year in MZ women and opposite-sex DZ twins, showing a positive association in the 1915-1959 birth cohort but no association in the 1960-1984 birth cohort. Conclusion Although associations are weak and somewhat inconsistent, our results suggest that intrauterine environment may play a role when explaining the association between birth weight and educational attainment.Peer reviewe

genetic and environmental factors on heart rate mean arterial pressure and carotid intima media thickness a longitudinal twin study

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima-media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/10 and 2014. Within-individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/cross-wave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time

Birth size and gestational age in opposite-sex twins as compared to same-sex twins: An individual-based pooled analysis of 21 cohorts

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister

Genetic and environmental factors affecting birth size variation: a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts

Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time

Association between birthweight and later body mass index: an individual-based pooled analysis of 27 twin cohorts participating in the CODATwins project

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m 2 higher BMI ( P  < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m 2 per kg birthweight, P  < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.Peer reviewe

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.Peer reviewe

Birth size and gestational age in opposite-sex twins as compared to same-sex twins : An individual-based pooled analysis of 21 cohorts

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95%Cl 18 to 45) heavier and 0.16 cm (95%CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95%Cl -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.Peer reviewe