Psychosocial Twin Cohort Studies in Japan: The Keio Twin Research Center (KoTReC).

The Keio Twin Research Center (KoTReC) was established in 2009 at Keio University to combine two longitudinal cohort projects - the Keio Twin Study (KTS) for adolescence and adulthood and the Tokyo Twin Cohort Project (ToTCoP) for infancy and childhood. KoTReC also conducted a two-time panel study of self-control and psychopathology in twin adolescence in 2012 and 2013 and three independent anonymous cross-sectional twin surveys (ToTcross) before 2012 - the ToTCross, the Junior and Senior High School Survey and the High School Survey. This article introduces the recent research designs of KoTReC and its publications.

Genetic and Environmental Influences on Traits of Gender Identity Disorder: A Study of Japanese Twins Across Developmental Stages.

The present study examined: (1) gender and age differences of mean gender identity disorder (GID) trait scores in Japanese twins; (2) the validity of the prenatal hormone transfer theory, which predicts that, in dizygotic (DZ) twin pairs, twins with an opposite-gender co-twin more frequently exhibit GID traits than twins with a same-gender co-twin; and (3) the magnitude of genetic and environmental influences on GID traits as a function of age and gender. Data from 1450 male twin pairs, 1882 female twin pairs, and 1022 DZ male-female pairs ranging from 3 to 26 years of age were analyzed. To quantify individual variances in GID traits, each participant completed four questionnaire items based on criteria for GID from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Our most important findings were: (1) Japanese females exhibited GID traits more frequently than males and Japanese children exhibited GID traits less frequently than adolescents and adults (among females, the prevalence was 1.6 % in children, 10 % in adolescents, and 12 % in adults; among males, the prevalence was 0.5, 2, and 3 %, respectively); (2) the data did not support the prenatal hormone transfer theory for GID traits; and (3) a large part of the variance for GID traits in children was accounted for by familial factors; however, the magnitude was found to be greater in children than in adolescents or adults, particularly among females. This study suggests that although the prevalence is likely to increase, familial effects are likely to decrease as individuals age.

Why children differ in motivation to learn: Insights from over 13,000 twins from 6 countries.

Little is known about why people differ in their levels of academic motivation. This study explored the etiology of individual differences in enjoyment and self-perceived ability for several school subjects in nearly 13,000 twins aged 9-16 from 6 countries. The results showed a striking consistency across ages, school subjects, and cultures. Contrary to common belief, enjoyment of learning and children's perceptions of their competence were no less heritable than cognitive ability. Genetic factors explained approximately 40% of the variance and all of the observed twins' similarity in academic motivation. Shared environmental factors, such as home or classroom, did not contribute to the twin's similarity in academic motivation. Environmental influences stemmed entirely from individual specific experiences.

Two cohort and three independent anonymous twin projects at the Keio Twin Research Center (KoTReC).

The Keio Twin Research Center has conducted two longitudinal twin cohort projects and has collected three independent and anonymous twin data sets for studies of phenotypes related to psychological, socio-economic, and mental health factors. The Keio Twin Study has examined adolescent and adult cohorts, with a total of over 2,400 pairs of twins and their parents. DNA samples are available for approximately 600 of these twin pairs. The Tokyo Twin Cohort Project has followed a total of 1,600 twin pairs from infancy to early childhood. The large-scale cross-sectional twin study (CROSS) has collected data from over 4,000 twin pairs, from 3 to 26 years of age, and from two high school twin cohorts containing a total of 1,000 pairs of twins. These data sets of anonymous twin studies have mainly targeted academic performance, attitude, and social environment. The present article introduces the research designs and major findings of our center, such as genetic structures of cognitive abilities, personality traits, and academic performances, developmental effects of genes and environment on attitude, socio-cognitive ability and parenting, genes x environment interaction on attitude and conduct problem, and statistical methodological challenges and so on. We discuss the challenges in conducting twin research in Japan.

The second to fourth digit ratio (2D:4D) in a Japanese twin sample: heritability, prenatal hormone transfer, and association with sexual orientation.

The second to fourth digit ratio has been argued to reflect prenatal hormonal influences and is reportedly associated with various psychological and behavioral traits, such as sexual orientation, cognitive abilities, and personality. We examined genetic and environmental influences on the second to fourth digit ratio (2D:4D) using a Japanese twin sample (N=300). The genetic analysis showed substantial additive genetic influences for both right and left hand 2D:4D. The rest of the variance was explained mainly by environmental influences not shared within twin pairs. These findings were, in general, in accordance with preceding studies with primarily Caucasian twin samples. The bivariate genetic analysis revealed that the additive genetic influences were largely shared between the right and left hand, while the non-shared environmental influences were largely unique to each hand. Results from a comparison of opposite-sex and same-sex twins were not significant, although they were in the predicted direction according to the prenatal hormone transfer hypothesis. Female monozygotic twin pairs discordant in sexual orientation showed significant within-pair differences in left hand 2D:4D, where non-heterosexual twins had lower (more masculinized) 2D:4D. In addition, we found that non-heterosexual male MZ twins had larger (more feminized) 2D:4D than their heterosexual co-twins. These results suggest the existence of non-shared environmental influences that affect both 2D:4D and sexual orientation.

Genetic and environmental sex differences in mental rotation ability: a Japanese twin study.

Sex differences in mental rotation ability have been observed in many countries. A previous study of Finnish participants reported that genetic and environmental influences on mental rotation ability differ between sexes. In this study, we assessed genetic and environmental influences on variance in mental rotation ability in 649 Japanese twins using a mental rotation test. To explain the influence of sex on variance in mental rotation ability, we applied genetic analysis using the sex limitation model. The following two factors explained variance in mental rotation ability: (1) the additive genetic factor, which reflects the accumulated small influence of many genes, and (2) the unique environmental factor, which is a type of environmental factor that differs between co-twins. The shared environmental factor, a type of environmental factor common for co-twins, could not explain the variance in mental rotation ability. Furthermore, the additive genetic factor was the same between sexes (i.e., not qualitative sex differences for the additive genetic factor), indicating that the same genes affect mental rotation ability in both sexes. Despite this observation, the additive genetic influence was greater in males than in females. In contrast, the unique environmental influence was not different between sexes. Considering the current results and those of a previous study, the quantitative sex difference for the additive genetic influences in mental rotation ability may be universal, while the unique environmental differences may depend on the characteristics of specific populations.

[Gender differences in genetic and environmental etiology of gender role personality (BSRI)].

This study investigated the possible effects of genetic and environmental gender differences in effect on individual differences by using the Bem Sex Role Inventory (BSRI) with twins. A sex/gender-limitation analysis, a behavior genetics methodology was used to the following: (a) effects of gender-specific genes, (b) gender differences in quantitative genetic effects, (c) effects of gender-specific shared environment, (d) gender differences of quantitative shared environment, and (e) gender differences of quantitative nonshared environment. Participants were adolescent and adult twins, including 111 identical male pairs, 241 identical female pairs, 36 fraternal male pairs, 65 fraternal female pairs, and 58 opposite-gender pairs. The results indicated that although masculinity and femininity were explained by genetic factors to some extent, there were no significant gender differences in the genetic factors. Moreover, because our data did not support a model which explained gender differences in the effects of specific common environment factors, no evidence was found to support the prenatal hormonal hypothesis or the existence of parenting which encouraged children's gender role personality.

Registry of adolescent and young adult twins in the Tokyo area.

Since established in 1998, the Keio Twin Project (KTP) has been dedicated to investigating genetic and environmental sources contributing to human psychological traits in adolescence and young adulthood. A population-based twin registry was constructed by the KTP through the use of official residential records in the Tokyo area, and to date requests to participate in our research have generated 1040 pairs of twins and triplets of age 14 to 30, forming one of the largest twin registries in Asia. Our comprehensive datasets, obtained through questionnaires, performance tests, and physical measurements, cover a wide range of human traits: personality, psychiatry, mental health, sociality, cognition, and physical index. Demographic variables and environment of upbringing are also sought by twins and by some parents. This extensive information allows us to clarify the genetic and environmental overlap across multiple traits as well as specificities unique to single traits. Adding an evolutionary psychology perspective to the behavior genetics framework is currently being attempted in order to develop a grand theory of human genetics.

Heritability of decisions and outcomes of public goods games.

Prosociality is one of the most distinctive features of human beings but there are individual differences in cooperative behavior. Employing the twin method, we examined the heritability of cooperativeness and its outcomes on public goods games using a strategy method. In two experiments (Study 1 and Study 2), twin participants were asked to indicate (1) how much they would contribute to a group when they did not know how much the other group members were contributing, and (2) how much they would contribute if they knew the contributions of others. Overall, the heritability estimates were relatively small for each type of decision, but heritability was greater when participants knew that the others had made larger contributions. Using registered decisions in Study 2, we conducted seven Monte Carlo simulations to examine genetic and environmental influences on the expected game payoffs. For the simulated one-shot game, the heritability estimates were small, comparable to those of game decisions. For the simulated iterated games, we found that the genetic influences first decreased, then increased as the numbers of iterations grew. The implication for the evolution of individual differences in prosociality is discussed.

Genetic Factors of Individual Differences in Decision Making in Economic Behavior: A Japanese Twin Study using the Allais Problem.

Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary) utility even when objective information of probabilities and reward are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more "rational." We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20-47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of "rational" decision making from the perspective of genetic correlations with cognitive abilities.

Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.

Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges because of the small effect sizes of individual genes. Phenotypically discordant monozygotic (MZ) twins provide a feasible way to minimize the effects of irrelevant genetic and environmental factors, and should yield more interpretable results by finding epigenetic or gene expression differences between twins. Here we conducted array-based genome-wide DNA methylation and gene expression analyses using 17 pairs of healthy MZ twins discordant intelligently. ARHGAP18, related to Rho GTPase, was identified in pair-wise methylation status analysis and validated via direct bisulfite sequencing and quantitative RT-PCR. To perform expression profile analysis, gene set enrichment analysis (GSEA) between the groups of twins with higher IQ and their co-twins revealed up-regulated expression of several ribosome-related genes and DNA replication-related genes in the group with higher IQ. To focus more on individual pairs, we conducted pair-wise GSEA and leading edge analysis, which indicated up-regulated expression of several ion channel-related genes in twins with lower IQ. Our findings implied that these groups of genes may be related to IQ and should shed light on the mechanism underlying human intelligence.