Genome-wide association study of male sexual orientation

Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10 -5 , including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10 -7 ) and 14 (p = 4.7 × 10 -7 ). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10 -3 ) for a SNP association previously reported (rs77013977, p = 7.1 × 10 -8 ), with the combined analysis yielding p = 6.7 × 10 -9 , i.e., a genome-wide significant association

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

Background: Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings: Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance: This indicated that a single latent variable influenced by a genetic component and common nonshared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders

Adolescents of the U.S. National Longitudinal Lesbian Family Study: Sexual Orientation, Sexual Behavior, and Sexual Risk Exposure

This study assessed Kinsey self-ratings and lifetime sexual experiences of 17-year-olds whose lesbian mothers enrolled before these offspring were born in the longest-running, prospective study of same-sex parented families, with a 93% retention rate to date. Data for the current report were gathered through online questionnaires completed by 78 adolescent offspring (39 girls and 39 boys). The adolescents were asked if they had ever been abused and, if so, to specify by whom and the type of abuse (verbal, emotional, physical, or sexual). They were also asked to specify their sexual identity on the Kinsey scale, between exclusively heterosexual and exclusively homosexual. Lifetime sexual behavior was assessed through questions about heterosexual and same-sex contact, age of first sexual experience, contraception use, and pregnancy. The results revealed that there were no reports of physical or sexual victimization by a parent or other caregiver. Regarding sexual orientation, 18.9% of the adolescent girls and 2.7% of the adolescent boys self-rated in the bisexual spectrum, and 0% of girls and 5.4% of boys self-rated as predominantly-to-exclusively homosexual. When compared with age- and gender-matched adolescents of the National Survey of Family Growth, the study offspring were significantly older at the time of their first heterosexual contact, and the daughters of lesbian mothers were significantly more likely to have had same-sex contact. These findings suggest that adolescents reared in lesbian families are less likely than their peers to be victimized by a parent or other caregiver, and that daughters of lesbian mothers are more likely to engage in same-sex behavior and to identify as bisexual

Autism spectrum disorders in adolescence and adulthood: Long-term outcomes and relevant issues for treatment and research

The advances in research and treatment of autism spectrum disorders (ASD) over the past three decades have focused largely on early childhood and school-age years. Although ASD is a lifelong condition, there has been relatively little attention paid to ASD during the adolescent and adulthood periods. As the population of those with ASD continues to rise and age, the need to provide research and treatment for this group has become increasingly evident. This paper reviews the current literature available on symptoms, functioning, and treatment of adolescents and adults with ASD, as well as the unique issues that arise for individuals with ASD after childhood. Adulthood outcomes for ASD are generally poor, even for those with average to above average cognitive ability. Further research and additional clinical resources are needed for this rapidly increasing group

Association of Maternal Diabetes Mellitus in Pregnancy With Offspring Adiposity Into Early Adulthood: Sibling study in a prospective cohort of 280,866 men from 248,293 families

BACKGROUND: Maternal diabetes in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so whether this is via intrauterine mechanisms or shared familial characteristics. METHODS AND RESULTS: A record linkage prospective cohort study of 280,866 singleton-born Swedish men from 248,293 families was used to explore the intrauterine effect of maternal diabetes on offspring body mass index (BMI) in early adulthood. Maternal diabetes during pregnancy was associated with greater mean BMI at age 18 in their sons. The difference in BMI was similar within brothers and between non-siblings. BMI of men whose mothers had diabetes during their pregnancy was on average 0.94kg/m(2) greater (95%CI: 0.35, 1.52) than in their brothers born before their mother was diagnosed with diabetes, after adjustment for birth year, maternal age, parity and education, birthweight, gestational age and age at assessment of BMI. Early-pregnancy BMI was positively associated with son’s BMI between non-siblings, but there was no association within brothers. Adjustment of the maternal diabetes-offspring BMI association for maternal BMI did not alter the association either within brothers or between non-siblings. Results were also robust to sensitivity analyses restricting the within sibling analyses to siblings born within 3 years of each other. CONCLUSION: Maternal diabetes has long-term consequences for greater BMI in offspring and this association is likely to be via intrauterine mechanisms and is independent of maternal BMI in early pregnancy

A Swedish national adoption study of criminality

Background To clarify the role of genetic and environmental factors in criminal behavior (CB), we examined all CB and violent and non-violent subtypes (VCB and NVCB, respectively) in a Swedish national sample of adoptees and their relatives. Method CB was defined by a conviction in the Swedish Crime Register with standard definitions for VCB and NVCB subtypes. We examined adoptees born 1950-1991 (n=18070) and their biological (n=79206) and adoptive (n=47311) relatives. Results The risk for all CB was significantly elevated in the adopted-away offspring of biological parents of which at least one had CB [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.4-1.6] and in the biological full and half-siblings of CB adoptees (OR 1.4, 95% CI 1.2-1.6 and OR 1.3, 95% CI 1.2-1.3, respectively). A genetic risk index (including biological parental/sibling history of CB and alcohol abuse) and an environmental risk index (including adoptive parental and sibling CB and a history of adoptive parental divorce, death, and medical illness) both strongly predicted probability of CB. These genetic and environmental risk indices acted additively on adoptee risk for CB. Moderate specificity was seen in the transmission of genetic risk for VCB and NVCB between biological parents and siblings and adoptees. Conclusions CB is etiologically complex and influenced by a range of genetic risk factors including a specific liability to CB and a vulnerability to broader externalizing behaviors, and by features of the adoptive environment including parental CB, divorce and death. Genetic risk factors for VCB and NVCB may be at least partially distinct