Jennifer R. Harris

The Body-Mass Index of Twins Who Have Been Reared Apart

To assess the relative importance of genetic and environmental effects on the body-mass index (weight in kilograms divided by the square of the height in meters), we studied samples of identical and fraternal twins, reared apart or reared together. The samples consisted of 93 pairs of identical twins reared apart, 154 pairs of identical twins reared together, 218 pairs of fraternal twins reared apart, and 208 pairs of fraternal twins reared together. The intrapair correlation coefficients of the values for body-mass index of identical twins reared apart were 0.70 for men and 0.66 for women. These are the most direct estimates of the relative importance of genetic influences (heritability) on the body-mass index, and they were only slightly lower than those for twins reared together in this and earlier studies. Similar estimates were derived from maximum-likelihood model-fitting analyses--0.74 for men and 0.69 for women. Nonadditive genetic variance made a significant contribution to the estimates of heritability, particularly among men. Of the potential environmental influences, only those unique to the individual and not those shared by family members were important, contributing about 30 percent of the variance. Sharing the same childhood environment did not contribute to the similarity of the body-mass index of twins later in life. We conclude that genetic influences on body-mass index are substantial, whereas the childhood environment has little or no influence. These findings corroborate and extend the results of earlier studies of twins and adoptees.

Heritability of Adult Body Height: A Comparative Study of Twin Cohorts in Eight Countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

Sex Differences in Heritability of BMI: A Comparative Study of Results from Twin Studies in Eight Countries

Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20-29 and 30-39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.

Individual differences in pain sensitivity: Genetic and environmental contributions

&NA; Large individual differences in pain sensitivity present a challenge for medical diagnosis and may be of importance for the development of chronic pain. Variance in pain sensitivity is partially mediated by genetic factors, but the extent of this contribution is uncertain. We examined cold‐pressor pain and contact heat pain in 53 identical (MZ) and 39 fraternal (DZ) twin pairs, and 4 single twins to determine the heritability of the two phenotypes, and the extent to which the same genetic and environmental factors affect both pain modalities. An estimated 60% of the variance in cold‐pressor pain and 26% of the variance in heat pain was genetically mediated. Genetic and environmental factors were only moderately correlated across pain modalities. Genetic factors common to both modalities explained 7% of the variance in cold‐pressor and 3% of the variance in heat pain. Environmental factors common to both modalities explained 5% of variance in cold‐pressor and 8% of the variance in heat pain. The remaining variance was due to factors that were specific to each pain modality. These findings demonstrate that cold‐pressor pain and contact heat pain are mainly distinct phenomena from both a genetic and an environmental standpoint. This may partly explain disparate results in genetic association studies and argues for caution in generalizing genetic findings from one pain modality to another. It also indicates that differences in pain scale usage account for a minor portion of the variance, providing strong support for the validity of subjective pain ratings as measures of experienced pain.

Prepublication data sharing.

Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.

Subjective well-being : genetic and environmental contributions to stability and change

BACKGROUND Previous cross-sectional studies have found substantial genetic influences on individual variation in subjective well-being (SWB), and evidence for sex-specific genetic effects has been reported. However, the genetic and environmental influences on stability and change in SWB over time are largely unexplored. METHOD Questionnaire data on SWB from a population-based sample of Norwegian twins born 1967 to 1979, initially surveyed in 1992 (T1) and re-surveyed in 1998 (T2), were analysed using structural equation modelling to explore the relative effects of genetic and environmental influences on phenotypic stability and change. RESULTS The phenotypic cross-time correlations for SWB were 0.51 and 0.49 for males and females respectively. The best-fitting longitudinal model specified only additive genetic and individual environmental effects with qualitative and quantitative sex-specific genetic influences. For both males and females, the additive genetic factors influencing SWB were largely stable, although some time-specific genetic contributions were indicated. Cross-time correlations for genetic effects were 0.85 and 0.78 for males and females respectively. The individual environmental influences were primarily time-specific. Additive genetic effects explained approximately 80% of the phenotypic cross-time correlation. For females, the magnitude of the additive genetic effects decreased significantly from T1 to T2, whereas for males, the estimates generally remained unchanged. CONCLUSIONS For both males and females, long-term stability of SWB was mainly attributable to stable additive genetic factors, whereas susceptibility to change was mostly related to individual environmental factors. However, both stable environmental contributions and emerging genetic influences were indicated.

Happiness and Health: Environmental and Genetic Contributions to the Relationship Between Subjective Well-Being, Perceived Health, and Somatic Illness

The aim was to identify genetic and environmental influences on the covariances between subjective well-being (SWB), perceived health, and somatic illness. Analyses were based on 6576 Norwegian twins aged 18-31. Heritabilities ranged from .24 to.66. SWB correlated .50 with perceived health, -.25 with musculoskeletal pain, and -.07 with allergy. Common genetic factors accounted for 45%-60% of associations. SWB and perceived health was to a high extent influenced by the same genes (r(g)=.72 and.82 for males and females, respectively). For SWB and musculoskeletal pain, r-sub(g) =-.29 and -.42 for males and females, respectively. Effects were partly sex specific. Environmental factors shared by twins did not affect the covariances. Results support a differentiated view of SWB-health relations, and imply that both genes and environment play important roles in the associations between well-being and health.

Irritable bowel syndrome in twins: genes and environment

Background and aims: Both environmental and genetic factors may contribute to irritable bowel syndrome (IBS). Nutrition in fetal life, an early environmental factor, seems to influence the development of chronic diseases later in life, such as coronary heart disease, hypertension, and non-insulin diabetes. This population based twin study evaluated the association between intrauterine growth, measured by weight and gestational age, and IBS. Structural equation analyses were conducted to analyse genetic and environmental sources of variation in liability to IBS. Methods: A postal questionnaire was sent to 12 700 Norwegian twins born between 1967 and 1979. The questionnaire included a checklist of 31 illnesses and symptoms, including IBS. The influence of birth weight on developing IBS was tested in four weight groups. Disease discordant monozygotic (MZ) pairs were analysed to test the association between intrauterine growth and IBS. Results: Concordance for IBS was significantly greater (p = 0.011) in monozygotic (22.4%) than in dizygotic (9.1%) twins. The heritability of IBS was estimated to be 48.4% among females. Birth weight below 1500 g (adjusted odds ratio 2.4 (95% confidence interval 1.1, 5.3)) contributed significantly to the development of IBS, which appeared 7.7 years earlier than in higher weight groups. In the MZ group with birth weights lower than 2500 g, twins with IBS were significantly lighter than twins without disease (190.6 g; p = 0.02). Conclusion: The present study demonstrates that restricted fetal growth has a significant influence on the development of IBS later in life. Weight below 1500 g influences age at onset. Genetic contribution appears to be important for IBS among females.

Combined Genome Scans for Body Stature in 6,602 European Twins: Evidence for Common Caucasian Loci

Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm).

The Norwegian Institute of Public Health Twin Panel: A Description of the Sample and Program of Research

The Norwegian Institute of Public Health in Oslo has an ongoing program of twin research using population-based cohorts of twins. The current database includes information on twins identified through the Medical Birth Registry of Norway and born from 1967-1979, altogether 15,370 twins. This is a longitudinal study with a cohort sequential design whereby new cohorts are recruited into the study at 5-6 year intervals. Sub-samples of these twins have participated in questionnaire studies and clinical assessment sub-projects. These projects include national and international collaborations. Our primary areas of interest include mental health and psychological well-being, obesity, asthma and allergies, health behaviors and health perceptions, comorbidity, and perinatal influences on health outcomes. This paper provides a brief overview of the data, sample, and the various research projects associated with this twin program of research.