We examined the contributions of genetic and environmental factors to body mass index (BMI) over approximately 28 years. Participants were 693 male, predominantly middle-class, twins (355 monozygotic, 338 dizygotic) from the Vietnam Era Twin Registry. The phenotypic correlation between age 20 and age 48 BMI was 0.52; the genetic correlation was 0.60. Most of the remaining variance at both times was accounted for by nonshared environmental factors. Since genetic factors are not perfectly correlated, this indicates that other genes affect BMI at one or both time points, leaving room for further exploration of the genetics of body mass stability. Mean BMI increased significantly from 22.7 (normal) to 27.8 (overweight). Overweight BMI at age 20 predicted midlife adult onset diabetes (adjusted odds ratio = 4.62, 95% CI 1.91 to 11.18), but not hypertension. Depending on one's vantage point, the results indicate elements of both stability and change in BMI. Very similar phenotypic and genetic correlations were observed over a similar time period in a WW II twin sample, but without the substantial mean increase in BMI. It seems unlikely that different genes influence BMI in the two cohorts. Therefore, we argue that nonshared environmental factors are probably primarily responsible for the secular increase in midlife BMI. Our results also provide prospective evidence that early excess BMI may have serious long-term health consequences, and that this risk is not limited to minorities or adults of lower socioeconomic status.

The common disease–common variant (CD–CV) hypothesis requires an explanation for the origin of the variation observed, since substantial neutral, but not deleterious, variation, that is, several alleles each at moderate to high frequency, can be maintained at any gene/locus by mutation. It is argued here that the guiding principle, not always stated, has been balancing selection, influenced by the wellestablished cases of deleterious alleles maintained through heterozygous advantage in the face of strong malarial selection against normal alleles. It is further argued that, although balanced polymorphisms have indeed arisen and reduced population loss through infectious disease, the history of balance in other contexts should have prevented acceptance of any hypothesis that generalized such a specific mechanism. Finally, it is suggested that in the present state of knowledge no single hypothesis for the genetical contribution to common disorders is justifiable.

The relative proportions of genetic and environmental variance in behavioral measures have been studied extensively. A growing body of literature has examined changes in heritability measures over time, but we are unaware of any prior efforts to assess developmental heritability changes for multiple behavioral phenotypes using multiple data sources. We have chosen to explore the proportional genetic influences on a variety of behaviors during the genetically and environmentally labile adolescent and young adult years. This meta-analysis examined 8 behavioral domains and incorporated only primary research articles reporting two or more heritability time points in order to minimize the age-to-age error variability. Linear regression analyses revealed significant cross-time heritability increases for externalizing behaviors, anxiety symptoms, depressive symptoms, IQ, and social attitudes and nonsignificant increases for alcohol consumption, and nicotine initiation, but no evidence of heritability changes for attention-deficit/hyperactivity disorder. A variety of mechanisms may underlie these findings including the rising importance of active genotype-environment correlation, an increase in gene expression, or proportional reductions in environmental variance. Additional longitudinal studies and the inclusion of measures of total variance in primary research reports will aid in distinguishing between these possibilities. Further studies exploring heritability changes beyond young adulthood would also benefit our understanding of factors influencing heritability of behavioral traits over the lifespan.

With the development of large twin-family registers worldwide (see the December 2006 issue of Twin Research and Human Genetics for an overview) new options for research projects become feasible, including longitudinal studies. In this special issue on Longitudinal Twin and Family Studies, several aspects of longitudinal research are highlighted and an overview of results is given from European, Australian and United States twin studies. These studies deal with a time span from birth to adulthood and a wide range of phenotypes is covered. Data collection in some studies is age/cohort driven; in others, subjects are followed from different ages at regular time intervals. Most studies are based on data collection in twins, but adoption and parent–offspring data designs are described as well. The overview of results of current longitudinal projects makes this special issue a reference resource for longitudinal research in developmental behavior genetics.

This article reviews the extant twin studies employing magnetic resonance imaging data (MRI), with an emphasis on studies of populationbased samples. There have been approximately 75 twin reports using MRI, with somewhat under half focusing on typical brain structure. Of these, most are samples of adults. For large brain regions such as lobar volumes, the heritabilities of large brain volumes are consistently high, with genetic factors accounting for at least half of the phenotypic variance. The role of genetics in generating individual differences in the volumes of small brain regions is less clear, mostly due to a dearth of information, but rarely because of disagreement between studies. Multivariate analyses show strong genetic relationships between brain regions. Cortical regions involved in language, executive function, and emotional regulation appear to be more heritable than other areas. Studies of brain shape also show significant, albeit lower, genetic effects on population variance. Finally, there is evidence of significant genetically mediated relationships between intelligence and brain structure. At present, the majority of twin imaging studies are limited by sample sizes small by the standards of behavioral genetics; nevertheless the literature at present represents a pioneering effort in the pursuit of answers to many challenging neurobiological questions.

The East Flanders Prospective Twin Survey, started in 1964, realised for the first time a population-based register of all multiple births in the Belgian Province of East Flanders, characterized by the systematic examination of the placenta and the accurate determination of zygosity based on blood groups, DNA and structure of fetal membranes. For decades, it has been the only register to include chorionicity in same-sex pairs of twins, an irreplaceable tool allowing almost certain diagnosis of monozygosity and the timing of the division of the zygote.in monozygotic twins. We showed that twins and triplets are far from being an homogenised group and demonstrated differences between these groups important enough to introduce these variables in the standard methodology of twin research. Examples are: Weinberg rule, sex ratio and duration of gestation.

Results obtained from previous longitudinal studies of reading difficulties indicate that reading deficits are generally stable. However, little is known about the etiology of this stability. Thus, the primary objective of this first longitudinal twin study of reading difficulties is to provide an initial assessment of genetic and environmental influences on the stability of reading deficits. Data were analyzed from a sample of 56 twin pairs, 18 identical (monozygotic, MZ) and 38 fraternal (dizygotic, DZ), in which at least one member of each pair was classified as reading-disabled in the Colorado Learning Disabilities Research Center, and on whom follow-up data were available. The twins were tested at two time points (average age of 10.3 years at initial assessment and 16.1 years at follow-up). A composite measure of reading performance (PIAT Reading Recognition, Reading Comprehension and Spelling) was highly stable, with a stability correlation of .84. Data from the initial time point were first subjected to univariate DeFries-Fulker multiple regression analysis and the resulting estimate of the heritability of the group deficit (h2g) was .84 (± .26). When the initial and follow-up data were then fitted to a bivariate extension of the basic DF model, bivariate heritability was estimated at .65, indicating that common genetic influences account for approximately 75% of the stability between reading measures at the two time points.

Impulsivity is a personality trait characterized by acting suddenly in an unplanned manner in order to satisfy a desire without consideration for the consequences of such behavior. There are several psychiatric disorders that include the term impulsivity as a criterion and, therefore, it has been suggested that impulsivity may be an important phenotype that may link a number of different behavioral disorders, including substance abuse. This study's aims were to determine if a significant association could be detected between the (AAT)n triplet repeat polymorphism as well as 5 single nucleotide polymorphisms (SNPs) in or near the CNR1 receptor gene and impulsivity in Southwest California ‘Mission’ Indians (SWC). Impulsivity was assessed using a scale derived from the Maudsley personality inventory, and blood samples were collected for DNA analyses from 251 individuals recruited from local Indian reservations. The estimated heritability (h2) for the impulsivity phenotype was 0.20 + 0.12 (p < .004). Impulsivity was significantly associated with the 6-repeat allele of the triplet repeat polymorphism (AATn/A6; p < .0001), as well as four SNPs in or near the CNR1 receptor gene: rs1535255 (p = .001), rs2023239 (p = .004), rs1049353 (p < .001) and rs806368 (p < .0006). These studies provide data to suggest that the CNR1 receptor gene may be significantly associated with impulsivity in SWC Indians.

The Netherlands Twin Register (NTR) was established around 1987 at the Vrije Universiteit in Amsterdam, the Netherlands. The current article summarizes the longitudinal genetic analyses of maternal and paternal ratings of twins' behavior as a function of the sex of the children for the traits of aggression (AGG), attention problems (AP), anxious/depression (ANX), internalizing behavior (INT) and externalizing behavior (EXT). We found that genetic influences are the most important factor in explaining individual differences in these traits. For most phenotypes, influences of genetic factors fluctuate throughout development, with the exception of AP, for which genetic influences remain of similar magnitude. Changes in genetic influences parallel those in shared environmental influences, while nonshared environmental influences remain relatively constant. Around 10% to 20% of the variance is accounted for by parent-specific shared environment, which includes rater bias. For all phenotypes, stability throughout childhood is accounted for by genetic and shared environmental factors, while nonshared environmental influences are mainly age/measurement specific. About 15% of the phenotypic stability is accounted for by rater-specific shared environmental influences, which include rater bias. In conclusion, between ages 3 and 12 genetic factors are the most important cause of individual differences in emotional and behavioral problems.

The objective of this study was to examine the heritability of an endophenotype relevant to nicotine dependence, namely tension reduction after smoking. This study also examined whether common genetic, shared environmental, and nonshared environmental factors influence this endophenotype measured repeatedly during an experimental paradigm. Twin and sibling pairs, all of whom were regular smokers, completed a laboratory paradigm in which they reported on levels of tension at baseline and after smoking each of 3 cigarettes. Univariate twin analyses suggested a sizeable role of additive genetic effects on tension reduction, with heritability estimates ranging between 47 and 68%. Result of multivariate Cholesky analyses indicated that there were additive genetic influences common to tension reduction assessed after cigarettes 1, 2, and 3. Multivariate models including genetic and nonshared environmental effects provided the best fit to the data. To the best of our knowledge, this is the first study to examine the genetic basis of a laboratory smoking endophenotype, in this case tension reduction after smoking. Implications for genetic association studies are discussed.

People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this dimension of personality can therefore give insights into the etiology of important psychiatric disorders. Neuroticism can be assessed easily via self-report questionnaires in large population samples. We have examined the genetic and phenotypic stability of neuroticism, measured up to 4 times over 22 years, on different scales, on a data set of 4999 families with over 20,000 individuals completing at least 1 neuroticism questionnaire. The neuroticism scales used were the Eysenck Personality Questionnaire revised (EPQ-R), the EPQ-R shortened form, and the NEO 5 factor inventory personality questionnaire. The estimates of heritability of the individual measures ranged from .26 ± .04 to .36 ± .03. Genetic, environmental, and phenotypic correlations averaged .91, .42, and .57 respectively. Despite the range in heritabilities, a more parsimonious ‘repeatability model’ of equal additive genetic variances and genetic correlations of unity could not be rejected. Use of multiple measures increases the effective heritability from .33 for a single measure to .43 for mean score because of the reduction in the estimate of the environmental variance, and this will increase power in genetic linkage or association studies of neuroticism.

In a normal delivery the second-born twin experiences a slight degree of hypoxia, which, as a rule, has no clinical importance. It is the oxygen debt everybody makes by running 30 metres.

The possibility of genotype–environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype–nonshared environment interactions. Multiple ‘variability genes’ were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2A and 5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to ‘contextualize’ the possible nonshared environmental influences for found gene–environment (G × E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G × E relationship observed for ESR1 and APOE and longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors.

Although social and intellectual engagement have been consistently associated with late-life functioning, rather than true causation, these associations may reflect the experiential choices of high functioning individuals (i.e., selection effects). We investigated the association of social activity with late-life physical functioning, cognitive functioning, and depression symptomatology using data from 1112 pairs of like-sex twins who participated in the Longitudinal Study of Aging Danish Twins. Consistent with previous research, we found that social activity was significantly correlated with overall level of physical functioning, cognitive functioning, and depression symptomatology. We also found that social activity was significantly and moderately heritable (estimate of .36), raising the possibility that its association with late-life functioning might reflect selection processes. Further, social activity did not predict change in functioning and in monozygotic twin pairs discordant on level of social activity, the more socially active twin was not less susceptible to age decreases in physical and cognitive functioning and increases in depression symptomatology than the less socially active twin. These results are interpreted in the context of the additional finding that nonshared environmental factors, although apparently not social activity, are the predominant determinant of changes in late-life functioning.

Girls who report first sexual intercourse during their early teen years have much higher rates of teenage pregnancy and childbearing than girls who delay sexual onset until older adolescence. In this study, we examine genetic and environmental influences on variation in teenage pregnancy and covariation with age at first sexual intercourse in two cohorts of Australian female twins. In the older twin cohort, born 1893–1964, we observe substantial heritable variation in teenage pregnancy that is largely shared with heritable variation in age at first sexual intercourse, with shared environment contributintablg little to variation in teenage pregnancy. Genetic influences on teenage pregnancy are smaller and nonsignificant in the younger twin cohort, born 1964–1971, where shared environment contributes much more and overlaps entirely with shared environmental variation in age at first intercourse.

Body-mass index (BMI), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels are known to be highly heritable. We evaluated the genetic and environmental relationships of these measures over time in an analysis of twin pairs. Monozygotic (235 pairs) and dizygotic (260 pairs) male twins were participants in the National Heart Lung and Blood Institute Veteran Twin Study, and were followed with three clinical exams from mean age 48 years to mean age 63 years. Structural equation modeling (SEM) with adjustment for APOE genotype (a significant contributor to TC and LDL-C) was used to assess longitudinal patterns of heritability. Results indicated a contribution of genetic factors to BMI, TC, LDL-C, HLD-C, and TG. Modest increases over time were observed in the heritability of BMI (from 0.48 to 0.61), TC (from 0.46 to 0.57), LDL-C (from 0.49 to 0.64), and HDL-C (from 0.50 to 0.62), but this trend was not present for TG. There was a corresponding decrease in shared environmental influences over time for these traits, although shared environment was a significant contributor only for HDL-C. Moreover, we observed that genetic influences for all measures were significantly correlated over time, and we found no evidence of age-specific genetic effects. In summary, longitudinal analyses of twin data indicate that genetic factors do not account for a significant proportion of the variation in age-related changes of BMI or lipid and lipoprotein levels.

Unlike-sex twins provide a unique natural experiment to investigate the influence of sex on gestation. Our data showed that length of gestation of unlike-sex pairs is similar to that of female same-sex pairs, and significantly (0.4 wks, p = .02) longer than that of male same-sex pairs. Birthweight of female unlike-sex twins was similar to female same-sex twins, but male unlike-sex twins weighed 78 g more than male same-sex twins ( p = .001). These data show that in unlikesex pairs it is the girl that prolongs gestation for her brother, resulting in a higher birthweight than that of same-sex boys.

Quantitative and molecular genetic research requires large samples to provide adequate statistical power, but it is expensive to test large samples in person, especially when the participants are widely distributed geographically. Increasing access to inexpensive and fast Internet connections makes it possible to test large samples efficiently and economically online. Reliability and validity of Internet testing for cognitive ability have not been previously reported; these issues are especially pertinent for testing children. We developed Internet versions of reading, language, mathematics and general cognitive ability tests and investigated their reliability and validity for 10- and 12-year-old children. We tested online more than 2500 pairs of 10-year-old twins and compared their scores to similar internet-based measures administered online to a subsample of the children when they were 12 years old (> 759 pairs). Within 3 months of the online testing at 12 years, we administered standard paper and pencil versions of the reading and mathematics tests in person to 30 children (15 pairs of twins). Scores on Internet-based measures at 10 and 12 years correlated .63 on average across the two years, suggesting substantial stability and high reliability. Correlations of about .80 between Internet measures and in-person testing suggest excellent validity. In addition, the comparison of the internet-based measures to ratings from teachers based on criteria from the UK National Curriculum suggests good concurrent validity for these tests. We conclude that Internet testing can be reliable and valid for collecting cognitive test data on large samples even for children as young as 10 years.

Association studies, comparing elite athletes with sedentary controls, have reported a number of genes that may be related to athlete status. The present study reports the first genome wide linkage scan for athlete status. Subjects were 4488 adult female twins from the TwinsUK Adult Twin Registry (793 monozygotic [MZ] and 1000 dizygotic [DZ] complete twin pairs, and single twins). Athlete status was measured by asking the twins whether they had ever competed in sports and what was the highest level obtained. Twins who had competed at the county or national level were considered elite athletes. Using structural equation modeling in Mx, the heritability of athlete status was estimated at 66%. Seven hundred DZ twin pairs that were successfully genotyped for 1946 markers (736 microsatellites and 1210 SNPs) were included in the linkage analysis. Identical-by-descent probabilities were estimated in Merlin for a 1 cM grid, taking into account the linkage disequilibrium of correlated SNPs. The linkage scan was carried out in Mx using the -approach. Suggestive linkages were found on chromosomes 3q22-q24 and 4q31-q34. Both areas converge with findings from previous studies using exercise phenotypes. The peak on 3q22-q24 was found at the SLC9A9 gene. The region 4q31-q34 overlaps with the region for which suggestive linkages were found in two previous linkage studies for physical fitness (FABP2 gene; Bouchard et al., 2000) and physical activity (UCP1 gene; Simonen et al., 2003). Future association studies should further clarify the possible role of these genes in athlete status.