A twin study of genetic and environmental influences on psychological traits of eating disorders in a Japanese female sample.

The purpose of the present study was to clarify genetic and environmental origins of psychological traits of eating disorders using a Japanese female twin sample. Participants were 162 pairs of female twins consisting of 116 pairs of monozygotic (MZ) twins and 46 pairs of dizygotic (DZ) twins in their adolescence. Psychological traits of eating disorders were assessed with five subscales of the Eating Disorder Inventory (EDI). As a result of using univariate twin analyses, among five subscales of EDI (maturity fears, ineffectiveness, interpersonal distrust, interoceptive awareness, and perfectionism), perfectionism showed significant additive genetic contributions and individual specific environmental effects. On the other hand, maturity fears, ineffectiveness, interoceptive awareness, and interpersonal distrust indicated significant shared environment contributions and individual specific environment effects. The results suggest the importance of both genetic and shared environmental influences on psychological traits of eating disorders in the present study.     

Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study

Background

Patients with the metabolic syndrome are more likely to develop type 2 diabetes and may have an increased risk of cardiovascular disease (CVD) events.We aimed to establish whether CVD event rates were influenced by the metabolic syndrome as defined by the World Health Organisation (WHO), the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) and to determine which component(s) of the metabolic syndrome (MS) conferred the highest cardiovascular risk in in 4900 patients with type 2 diabetes allocated to placebo in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.

Research design and methods

We determined the influence of MS variables, as defined by NCEP ATPIII, IDF and WHO, on CVD risk over 5 years, after adjustment for CVD, sex, HbA_1c, creatinine, and age, and interactions between the MS variables in a Cox proportional-hazards model.

Results

About 80% had hypertension, and about half had other features of the metabolic syndrome (IDF, ATPIII). There was no difference in the prevalence of metabolic syndrome variables between those with and without CVD at study entry. The WHO definition identified those at higher CVD risk across both sexes, all ages, and in those without prior CVD, while the ATPIII definition predicted risk only in those aged over 65 years and in men but not in women. Patients meeting the IDF definition did not have higher risk than those without IDF MS. CVD risk was strongly influenced by prior CVD, sex, age (particularly in women), baseline HbA1_c, renal dysfunction, hypertension, and dyslipidemia (low HDL-c, triglycerides > 1.7 mmol/L). The combination of low HDL-c and marked hypertriglyceridemia (> 2.3 mmol/L) increased CVD risk by 41%. Baseline systolic blood pressure increased risk by 16% per 10 mmHg in those with no prior CVD, but had no effect in those with CVD. In those without prior CVD, increasing numbers of metabolic syndrome variables (excluding waist) escalated risk.

Conclusion

Absence of the metabolic syndrome (by the WHO definition) identifies diabetes patients without prior CVD, who have a lower risk of future CVD events. Hypertension and dyslipidemia increase risk.     

Education modifies genetic and environmental influences on BMI

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height(2)) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were -.13 in women, -.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity.     

Genetic and environmental influences on migraine: a twin study across six countries.

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.     

Intrinsic and extrinsic religiousness: genetic and environmental influences and personality correlates.

This report presents findings for the Intrinsic (IR) and Extrinsic (ER) religiousness scales from the Minnesota Study of Twins Reared Apart. The scales were shown to be internally consistent, sufficiently distinct from the scales of the California Psychological Inventory and the Multidimensional Personality Questionnaire and unrelated to a number of measures of response style to justify treating them as distinct traits. The I scales also showed considerable evidence of construct validity in its correlations with religious fundamentalism and authoritarianism as assessed by the MMPI and Altemeyer's Right-Wing Authoritarianism scale. Data on IR and ER from 35 pairs of monozygotic twins reared apart (MZA) and 37 pairs of dizygotic twins reared apart (DZA) were fitted to a biometric model and demonstrated significant heritability (0.43 and 0.39), with a model containing genetic plus environmental factors fitting significantly better than a model containing only an environmental component. Twin similarity could not be explained by placement on a self-reported measure of family Moral Religious Emphasis as measured by the Family Environment Scale.     

Cleft lip and palate: understanding genetic and environmental influences

Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.     

Childhood obesity: genetic and environmental overlap with normal-range BMI

Objective: To understand the overlap between the etiology of obesity and normal variation in BMI in children. Methods and Procedures: Height and weight data were available from a large UK representative sample of twins: 2,342 same‐sex pairs at 7 years and 3,526 same‐sex pairs at 10 years. The twin method and model‐fitting techniques were used to estimate genetic and environmental contributions to BMI. DeFries‐Fulker (DF) extremes analysis was used to investigate genetic and environmental influences on the mean difference between obese and normal‐weight children. Obesity was classified using the International Obesity Task Force (IOTF) criteria. Results: At both ages, BMI and obesity were highly heritable (0.60–0.74) and only modestly influenced by shared environmental factors (0.12–0.22). Extremes analyses indicated that genetic and environmental influences on obesity are quantitatively and qualitatively similar to those operating across the range of BMI. Discussion: Obesity is the extreme of the same genetic and environmental factors responsible for variation throughout the distribution of BMI. This finding implies that genes that influence obesity will also be associated with BMI in the normal range, and similar environmental influences will affect BMI in the clinical and normal range. Knowing that obesity is influenced by the same genetic and environmental factors that affect weight at all levels has implications for investigating the mechanisms for weight gain and developing interventions for weight control.     

Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db/db mouse, or at the peptide level, as in ob/ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka-Long-Evans-Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.     

A twin study of genetic influences on epilepsy outcome.

The identification of genetic factors that confer susceptibility to the epilepsies has to date been the focus of genetic efforts in this field. Few studies have assessed the genetic contribution to disease course in epilepsy, yet an understanding of the genetic influences on epilepsy outcome is key to developing new therapeutic strategies. The aim of this study was to assess the genetic contributions to epilepsy outcome in twin pairs concordant for epilepsy. We studied 37 epilepsy concordant twin pairs (27 monozygotic, 10 dizygotic) in whom there were no recognized environmental contributions (e.g., acquired brain injury) to epilepsy, and in whom the most likely cause for epilepsy was a shared genetic susceptibility. Clinical outcome was determined using the binary measure of Seizure Status (seizure remission or recurrence) and on a six-category ordinal Outcome Scale. Epilepsy outcome was independent of age of seizure onset, age at assessment and major epilepsy syndrome diagnosis. The proportion of twin pairs concordant for Seizure Status was 0.81 (22/27) for monozygous and 1.0 (10/10) for dizygous pairs, p = 0.3. Within-pair correlation in outcome (Outcome Scale) was 0.60 (95% CI: 0.32, 0.78) in monozygous and 0.78 (0.48, 0.92) in dizygous pairs. These data provide no evidence for genetic influences on epilepsy outcome independent of those that contribute to disease susceptibility. The observed high correlations for outcome suggest that, for epilepsy, susceptibility genes also have a major influence on outcome.     

Stability and change in genetic and environmental influences on hand-grip strength in older male twins.

The aim of this study was to investigate aging-related changes in the contribution of genetic and environmental influences to hand-grip strength in late adulthood. Subjects in this study are 152 intact twin pairs (77 monozygotic and 75 dizygotic pairs) from the National Heart, Lung, and Blood Institute Twin Study assessed repeatedly for hand-grip strength at mean ages of 63 and 73 yr. Structural equation genetic modeling was used to investigate stability and change in the genetic and environmental components of variance of hand-grip strength in late adulthood. Average decline in strength over the 10 yr of follow-up was -1.05+/-6.8 (SD) kg and was highly significant (P = 0.003). The test-retest correlation between baseline and follow-up grip strength was 0.62 (P<0.001). Bivariate genetic modeling found significant genetic and shared environmental stability in hand-grip strength over the 10 yr of follow-up, with genetic and shared environmental influences accounting for 35 and 48%, respectively, of the test-retest phenotypic correlation. We conclude from these results that stability in hand-grip strength in late adulthood is due primarily to continuity of genetic and familial influences.     

GenomEUtwin: a strategy to identify genetic influences on health and disease.

In this issue of Twin Research, we describe different facets of a European Community funded effort, GenomEUtwin, which capitalises on eight of the world's largest and best characterised twin registers and a multi-national population cohort, MORGAM. This international study, reaching beyond the geographical borders of Europe, is based on linkage and association strategies designed to identify genetic contributors to health and disease using integrated expertise of participating groups in genetics, epidemiology and biostatistics. By merging information from numerous epidemiological and genetic databases, GenomEUtwin will create an intellectual and technical infrastructure for future genetic epidemiological studies aiming to define genetic and life style risks for common human diseases.     

Shared aetiology of risky sexual behaviour and adolescent misconduct: genetic and environmental influences

Risky sexual behaviour (RSB) is a major risk factor for serious diseases as well as unplanned pregnancy. It is not known if RSB has a genetic basis or if it is only influenced by social and cultural conditions. Adolescent conduct disorder has previously been linked to RSB and has been found to be influenced by both genetic and environmental factors. In this study, we look at normal variation in a broad measure of RSB and in retrospectively reported adolescent misconduct in a large community sample of twins ( n  = 4904) to partition the variance and covariance between the traits into genetic and environmental components. We found that RSB is influenced to the same extent by genes, shared environment and unshared environment. Adolescent misconduct is moderately influenced by genetic factors and only modestly by shared environmental factors. Moreover, RSB is associated with adolescent misconduct ( r  = 0.5), primarily because of genetic correlation between the variables. The implications of our findings as well as possible sex differences are discussed.     

Age at maturity in wild baboons: genetic, environmental and demographic influences

The timing of early life-history events, such as sexual maturation and first reproduction, can greatly influence variation in individual fitness. In this study, we analysed possible sources of variation underlying different measures of age at social and physical maturation in wild baboons in the Amboseli basin, Kenya. The Amboseli baboons are a natural population primarily comprised of yellow baboons (Papio cynocephalus) that occasionally hybridize with anubis baboons (Papio anubis) from outside the basin. We found that males and females differed in the extent to which various factors influenced their maturation. Surprisingly, we found that male maturation was most strongly related to the proportion of anubis ancestry revealed by their microsatellite genotypes: hybrid males matured earlier than yellow males. In contrast, although hybrid females reached menarche slightly earlier than yellow females, maternal rank and the presence of maternal relatives had the largest effects on female maturation, followed by more modest effects of group size and rainfall. Our results indicate that a complex combination of demographic, genetic, environmental, and maternal effects contribute to variation in the timing of these life-history milestones.     

Role of genetic and environmental influences on heart rate variability in middle-aged men

Our aim was to estimate causal relationships of genetic factors and different specific environmental factors in determination of the level of cardiac autonomic modulation, i.e., heart rate variability (HRV), in healthy male twins and male twins with chronic diseases. The subjects were 208 monozygotic (MZ, 104 healthy) and 296 dizygotic (DZ, 173 healthy) male twins. A structured interview was used to obtain data on lifetime exposures of occupational loading, regularly performed leisure-time sport activities, coffee consumption, smoking history, and chronic diseases from 12 yr of age through the present. A 5-min ECG at supine rest was recorded for the HRV analyses. In univariate statistical analyses based on genetic models with additive genetic, dominance genetic, and unique environmental effects, genetic effects accounted for 31-57% of HRV variance. In multivariate statistical analysis, body mass index, percent body fat, coffee consumption, smoking, medication, and chronic diseases were associated with different HRV variables, accounting for 1-11% of their variance. Occupational physical loading and leisure-time sport activities did not account for variation in any HRV variable. However, in the subgroup analysis of healthy and diseased twins, occupational loading explained 4% of the variability in heart periods. Otherwise, the interaction between health status and genetic effects was significant for only two HRV variables. In conclusion, genetic factors accounted for a major portion of the interindividual differences in HRV, with no remarkable effect of health status. No single behavioral determinant appeared to have a major influence on HRV. The effects of medication and diseases may mask the minimal effect of occupational loading on HRV.     

Determinants of hierarchical genetic structure in Atlantic salmon populations: environmental factors vs. anthropogenic influences

Disentangling the effects of natural environmental features and anthropogenic factors on the genetic structure of endangered populations is an important challenge for conservation biology. Here, we investigated the combined influences of major environmental features and stocking with non‐native fish on the genetic structure and local adaptation of Atlantic salmon (Salmo salar) populations. We used 17 microsatellite loci to genotype 975 individuals originating from 34 French rivers. Bayesian analyses revealed a hierarchical genetic structure into five geographically distinct clusters. Coastal distance, geological substrate and river length were strong predictors of population structure. Gene flow was higher among rivers with similar geologies, suggesting local adaptation to geological substrate. The effect of river length was mainly owing to one highly differentiated population that has the farthest spawning grounds off the river mouth (up to 900 km) and the largest fish, suggesting local adaptation to river length. We detected high levels of admixture in stocked populations but also in neighbouring ones, implying large‐scale impacts of stocking through dispersal of non‐native individuals. However, we found relatively few admixed individuals suggesting a lower fitness of stocked fish and/or some reproductive isolation between wild and stocked individuals. When excluding stocked populations, genetic structure increased as did its correlation with environmental factors. This study overall indicates that geological substrate and river length are major environmental factors influencing gene flow and potential local adaptation among Atlantic salmon populations but that stocking with non‐native individuals may ultimately disrupt these natural patterns of gene flow among locally adapted populations.     

Genetic and environmental influences on pupil performances.

The results presented in this paper are part of a current comparative study of genetic and environmental influences in three educational settings: Stockholm, Jerusalem and the Israeli kibbutz. We specifically wanted to investigate whether a more restrictive educational setting would decrease genetic influences. Here we report on comparisons of cognitive performance measures at several time points for twins/controls, boys/girls and within-pair similarity in MZ, DZ and controls. The tests used were the Raven Progressive Matrices, verbal, reading comprehension and arithmetic. The results show no differences between twins and controls, whilst gender differences seem to be smallest in the Stockholm sample and largest in Jerusalem. A pattern of genetic influences on cognitive performance was also clearly visible in Jerusalem. In Stockholm shared environmental influences at home and at school seemed even stronger than in the kibbutz. No consistent differences were found between tests or occasions.     

Genetic and environmental influences on a measure of infant attachment security.

A twin study of infant attachment security at age 24 months was conducted on archival data for a sample of 99 MZ pairs and 108 DZ pairs from the Louisville Twin Study. MZ concordance for attachment was 62.6%, which was significantly greater than the DZ concordance of 44.4%. Concordances were transformed into polychoric correlations, and LISREL was used to conduct a quantitative genetic analysis of the data. Results indicated that 25% of the variability in attachment was attributable to genetic factors, and the remaining 75% was attributable to non-shared environmental effects. No evidence was found for a contribution from shared environmental influences to attachment security. Possible concerns about the validity of twin methodology are addressed and various interpretations of the results are presented.     

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.