Aline Jelenkovic

Genetic and environmental influences on growth from late childhood to adulthood: a longitudinal study of two Finnish twin cohorts.

Objectives: Human growth is a complex process that remains insufficiently understood. We aimed to analyze genetic and environmental influences on growth from late childhood to early adulthood.

The association between height and birth order: evidence from 652,518 Swedish men.

Background Birth order is associated with outcomes such as birth weight and adult socioeconomic position (SEP), but little is known about the association with adult height. This potential birth order-height association is important because height predicts health, and because the association may help explain population-level height trends. We studied the birth order-height association and whether it varies by family characteristics or birth cohort. Methods We used the Swedish Military Conscription Register to analyse adult height among 652 518 men born in 1951–1983 using fixed effects regression models that compare brothers and account for genetic and social factors shared by brothers. We stratified the analysis by family size, parental SEP and birth cohort. We compared models with and without birth weight and birth length controls. Results Unadjusted analyses showed no differences between the first two birth orders but in the fixed effects regression, birth orders 2, 3 and 4 were associated with 0.4, 0.7 and 0.8 cm (p<0.001 for each) shorter height than birth order 1, respectively. The associations were similar in large and small and high-SEP and low-SEP families, but were attenuated in recent cohorts. Birth characteristics did not explain these associations. Conclusions Birth order is an important determinant of height. The height difference between birth orders 3 and 1 is larger than the population-level height increase achieved over 10 years. The attenuation of the effect over cohorts may reflect improvements in living standards. Decreases in family size may explain some of the secular-height increases in countries with decreasing fertility.

Association of Birth Order with Cardiovascular Disease Risk Factors in Young Adulthood: A Study of One Million Swedish Men

Background Birth order has been suggested to be linked to several cardiovascular disease (CVD) risk factors, but the evidence is still inconsistent. We aim to determine the associations of birth order with body mass index (BMI), muscle strength and blood pressure. Further we will analyse whether these relationships are affected by family characteristics. Methods BMI, elbow flexion, hand grip and knee extension strength and systolic and diastolic blood pressure were measured at conscription examination in 1 065 710 Swedish young men born between 1951 and 1975. The data were analysed using linear multivariate and fixed effects regression models; the latter compare siblings and account for genetic and social factors shared by brothers. Results Fixed effect regression analysis showed that birth order was inversely associated with BMI: second and third born had 0.8% and 1.1% (p<0.001) lower BMI than first-born, respectively. The association pattern differed among muscle strengths. After adjustment for BMI, first-born presented lower elbow flexion and hand grip strength than second-born (−5.9 N and −3.8 N, respectively, p<0.001). Knee extension strength was inversely related to birth order though not always significantly. The association between birth order and blood pressure was not significant. Conclusions Birth order is negatively associated with BMI and knee extension strength, positively with elbow flexion and hand grip strength, and is not associated with blood pressure among young men. Although the effects are small, the link between birth order and some CVD risk factors is already detectable in young adulthood.

Quantitative genetics of human morphology and obesity-related phenotypes in nuclear families from the Greater Bilbao (Spain): Comparison with other populations

Background: It is well established that variation of soft-tissue traits is less influenced by the genetic component than skeletal traits. However, it is still unclear whether heritabilities (h2) of obesity-related phenotypes present a common pattern across populations. Aim: To estimate familial resemblance and heritability of body size, shape and composition phenotypes and to compare these results with those from other populations. Subjects and methods: The subject group consisted of 533 nuclear families living in Greater Bilbao and included 1702 individuals aged 2–61 years. Familial correlations and h2 were estimated for 29 anthropometric phenotypes (19 simple measures, three derived factors, four obesity indices and the three Heath-Carter somatotype components) using MAN and SOLAR programmes. Results: All phenotypes were influenced by additive genetic factors with narrow sense heritabilities ranging from 0.28–0.69. In general, skeletal traits exhibited the highest h2, whereas phenotypes defining the amount of adipose tissue, particularly central fat, were less determined by genetic factors. Conclusions: Familial correlations and heritability estimates of body morphology and composition from the Greater Bilbao sample were within the range observed in other studies. The lower heritability detected for central fat has also been found in some other populations, but further investigations in different populations using the same anthropometric traits and estimation methods are needed in order to obtain more robust conclusions.

Association of paternal IQ in early adulthood with offspring mortality and hospital admissions for injuries: a cohort study of 503 492 Swedish children

Background Higher intelligence (IQ) has been related to a lower risk of mortality and hospital admissions for injuries, but little is known about the effect of parental IQ on offspring outcomes. We explored associations of paternal IQ with mortality and hospitalisations for injuries from all external causes in offspring. Methods A cohort of 503 492 Swedish children under 5 years of age with information on paternal IQ was obtained by record linkage of national registers. HR with 95% CIs were estimated using Cox regression. Results There was some evidence that paternal IQ was inversely associated with total and external-cause mortality in offspring, although the effects were modest and disappeared when controlling for parents’ socioeconomic position (SEP). The only robust gradient was found between paternal IQ and hospital admissions for injuries (HRper 1-SD increase in IQ 0.93, 95% CI 0.92 to 0.94; p<0.001), which was slightly attenuated but retained statistical significance after adjustment for SEP (0.95, 95% CI 0.94 to 0.97; p<0.001). Conclusions Children to fathers with lower IQ may have an increased risk of injury by external causes. Messages on family safety and injury prevention might be tailored according to parental cognitive abilities.

Contribution of genetics and environment to craniofacial anthropometric phenotypes in Belgian nuclear families.

Abstract In this study we estimate relative genetic and environmental influences on head-related anthropometric phenotypes. The subject group consisted of 119 nuclear families living in Brussels, Belgium, and included 238 males and 236 females, ages 17 to 72 years. Two factor analyses with vari-max rotation (the first one related to facial measurements and the second one to overall head morphology) were used to analyze 14 craniofacial size traits. The resulting four synthetic traits [HFCF, VFCF, HDF1, and HDF2—horizontal (breadth) and vertical (height) facial factors and two head horizontal (breadth) factors, respectively] were used as summary variables. Maximum heritabilities (H2) were estimated for all studied traits, and variance components analysis was applied to determine the contribution of genetics and environment on the four craniofacial factors. In addition, we examined the covariations between the face (HFCF and VFCF) and head-related factors (HDF1 and HDF2), separately. Quantitative genetic analysis showed that HFCF, VFCF, HDF1, and HDF2 variation was appreciably attributable to additive genetic effects, with heritability (h2) estimates of 67.62%, 54.97%, 70.76%, and 65.05%, respectively. The three variance components reflecting a shared familial environment were nonsignificant for these four phenotypes. Bivariate analysis revealed significant additive and residual correlations for both pair of traits. The results confirm the existence of a significant genetic component determining the four craniofacial synthetic traits, and common genetic and environmental effects shared by the two face-related phenotypes and by the head-related ones.

Association between serum fatty acids and lipoprotein subclass profile in healthy young adults: Exploring common genetic and environmental factors

OBJECTIVE Little is known about the associations of serum fatty acids with lipoprotein profile and the underlying genetic and environmental etiology of these relationships. We aimed to analyze the phenotypic association of serum n-6 and n-3 polyunsaturated (PUFAs), monounsaturated (MUFAs) and saturated (SFAs) fatty acids (relative proportion to total fatty acids) with lipids and lipoproteins, and to quantify common genetic and environmental factors determining their covariation. METHODS Two cohorts of healthy Finnish twins were assessed in young adulthood. Data were available for 1269 individual twins including 561 complete pairs. Serum metabolites were measured by nuclear magnetic resonance spectroscopy. Bivariate quantitative genetic models were used to decompose the phenotypic covariance between the pairs of traits into genetic and environmental components. RESULTS Among the strongest correlations observed, serum total n-6 PUFAs and linoleic acid were inversely (max. r=-0.65) and MUFAs positively (max. r=0.63) correlated with triglycerides and very low-density lipoprotein (VLDL) particle concentration, particularly with large VLDL (for n-6 PUFAs) and medium VLDL (for MUFAs). Genetic factors significantly contributed to their covariance with bivariate heritability estimates ranging from 44% to 56% for n-6 PUFAs and 58% to 66% for MUFAs. Genetic correlations with lipid traits were moderate to high (max. rA=-0.59 and 0.70 for n-6 PUFAs and MUFAs, respectively). Statistically significant, but substantially weaker phenotypic correlations of total n-3 PUFAs, docosahexaenoic acid (DHA) and SFAs with lipoprotein profile were not decomposed into their genetic and environmental components. CONCLUSION Shared genetic factors are important in explaining why higher concentrations of serum n-6 PUFAs and lower concentrations of serum MUFAs strongly associate with lower triglyceride and VLDL particle concentrations.

A statistical investigation into the sharing of common genetic factors between blood pressure and obesity phenotypes in nuclear families from the Greater Bilbao (Spain).

Objectives Several obesity phenotypes (e.g. body mass and fat, fat distribution) have been suggested to be a risk for elevated blood pressure. This study was undertaken to determine the heritability of four blood pressure phenotypes: SBP, DBP, pulse pressure (PP) and mean arterial pressure (MAP) and to assess the strength of genetic and environmental correlations among these phenotypes, and also between blood pressure and the different obesity-related traits. Methods The studied sample consisted of 429 nuclear families living in the Greater Bilbao (Spain) and included 1302 individuals aged 4–61 years. Univariate and bivariate quantitative genetic analyses were performed using a variance components procedure implemented in Sequential Oligogenic Linkage Analysis Routines software. Results SBP, DBP, PP and MAP were significantly influenced by genetic factors with heritability estimates of 0.25, 0.28, 0.14 and 0.31, respectively, and presented high genetic and environmental correlations between them (except DBP–PP). On the contrary, whereas SBP, DBP and MAP showed common environmental factors with almost all body mass and fat-related traits, pleiotropic effects were only detected for some pairs, especially for those phenotypes that included skinfolds. In contrast, PP did not exhibit common genetic or environmental factors with obesity phenotypes in the studied population Conclusion Blood pressure and obesity phenotypes do not share, in general, a substantial influence of common genetic and environmental effects. Finally, the results obtained revealed the importance of the amount of adipose tissue in the genetic correlations with SBP, DBP and MAP, at least, during the growth period.

Common genetic and environmental factors among craniofacial traits in Belgian nuclear families: comparing skeletal and soft-tissue related phenotypes.

The major objective of this study was to determine the possible effects of common genetic and environmental factors among 18 craniofacial anthropometric traits, with special attention to the differences between skeletal and soft-tissue related phenotypes. The studied sample consisted of 122 nuclear families living in Brussels and included 251 males and 258 females aged from 13 to 72 years. Univariate and bivariate quantitative genetic analyses were performed using a variance components procedure implemented in SOLAR software. All phenotypes were significantly influenced by additive genetic factors with heritability estimates ranging from 0.46 (nose height) to 0.72 (external biocular breadth). Sex, age and their interactions explained 7-46% of the total phenotypic variance of the traits. Bivariate analysis revealed that several traits share a common genetic and/or environmental basis while other traits show genetic and environmental independence from one another. More and greater genetic and environmental correlations were observed among skeletal phenotypes, than among soft-tissue traits and between both categories. Apart from the tissue composition, other characteristics of the craniofacial morphology such as the orientation (e.g. heights, breadths) have shown to be important factors in determining pleiotropy and common environmental effects between some pairs of traits. In conclusion, the results confirm that overall head configuration is largely determined by additive genetic effects, and that common genetic and environmental factors affecting craniofacial size and shape are stronger for the skeletal traits than for the soft-tissue traits.

Heritability variations of body linearity and obesity indicators during growth.

Longitudinal as well as cross-sectional studies have shown variations with age in heritability estimates for body dimensions from infancy to adulthood, even though the patterns of variation are not completely clear. Further study on this subject is of great interest and may help obesity interventions for preventing or treating obesity in children. Therefore, the aim of the present study is to analyse the changes in the genetic and environmental architecture of 8 body linearity and obesity-related phenotypes during the growth process in a cross-sectional sample of 1018 nuclear families from the province of Biscay (Basque Country, Spain). The contribution of additive genetic effects to the variation of the analysed traits was estimated by a variance component analysis using the SOLAR program. Moderate to high heritability estimates were obtained for all 8 anthropometric phenotypes (38.23-65.98%). The heritability values show an increasing trend with age and in the course of the entire ontogenetic development two age periods were remarkable. At 7(+)-8(+) years of age a strong increase in heritability estimates was found for all the anthropometric phenotypes, except for the sum of skinfolds (SF6), reflecting the biological significance of genes during mid-childhood. During puberty, most of the obesity related phenotypes showed their highest heritability values while linear measurements and weight presented a decrease in the genetic contributions. In conclusion, this study confirms that additive genetic influences have a considerable effect on body linearity and obesity-related traits throughout the growth period and that mid-childhood and puberty are very sensitive periods in human life cycle.