●.Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior


Andrea Ganna et al., Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior. Science 365. eaat7693(2019).

內容取自:https://science.sciencemag.org/content/365/6456/eaat7693

Abstract

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual’s sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.

 

Structured Abstract

INTRODUCTION

Across human societies and in both sexes, some 2 to 10% of individuals report engaging in sex with same-sex partners, either exclusively or in addition to sex with opposite-sex partners. Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for the specific genes involved have been underpowered to detect effect sizes realistic for complex traits.

RATIONALE

For the first time, new large-scale datasets afford sufficient statistical power to identify genetic variants associated with same-sex sexual behavior (ever versus never had a same-sex partner), estimate the proportion of variation in the trait accounted for by all variants in aggregate, estimate the genetic correlation of same-sex sexual behavior with other traits, and probe the biology and complexity of the trait. To these ends, we performed genome-wide association discovery analyses on 477,522 individuals from the United Kingdom and United States, replication analyses in 15,142 individuals from the United States and Sweden, and follow-up analyses using different aspects of sexual preference.

RESULTS

In the discovery samples (UK Biobank and 23andMe), five autosomal loci were significantly associated with same-sex sexual behavior. Follow-up of these loci suggested links to biological pathways that involve sex hormone regulation and olfaction. Three of the loci were significant in a meta-analysis of smaller, independent replication samples. Although only a few loci passed the stringent statistical corrections for genome-wide multiple testing and were replicated in other samples, our analyses show that many loci underlie same-sex sexual behavior in both sexes. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in male and female same-sex sexual behavior, and the genetic influences were positively but imperfectly correlated between the sexes [genetic correlation coefficient (rg)= 0.63; 95% confidence intervals, 0.48 to 0.78]. These aggregate genetic influences partly overlapped with those on a variety of other traits, including externalizing behaviors such as smoking, cannabis use, risk-taking, and the personality trait “openness to experience.” Additional analyses suggested that sexual behavior, attraction, identity, and fantasies are influenced by a similar set of genetic variants (rg > 0.83); however, the genetic effects that differentiate heterosexual from same-sex sexual behavior are not the same as those that differ among nonheterosexuals with lower versus higher proportions of same-sex partners, which suggests that there is no single continuum from opposite-sex to same-sex preference.

CONCLUSION

Same-sex sexual behavior is influenced by not one or a few genes but many. Overlap with genetic influences on other traits provides insights into the underlying biology of same-sex sexual behavior, and analysis of different aspects of sexual preference underscore its complexity and call into question the validity of bipolar continuum measures such as the Kinsey scale. Nevertheless, many uncertainties remain to be explored, including how sociocultural influences on sexual preference might interact with genetic influences. To help communicate our study to the broader public, we organized workshops in which representatives of the public, activists, and researchers discussed the rationale, results, and implications of our study.

圖片下載

A genome-wide association study (GWAS) of same-sex sexual behavior reveals five loci and high polygenicity. Follow-up analyses show potential biological pathways; show genetic correlations with various traits; and indicate that sexual preference is a complex, heterogeneous phenotype.

A genome-wide association study (GWAS) of same-sex sexual behavior reveals five loci and high polygenicity.
Follow-up analyses show potential biological pathways; show genetic correlations with various traits; and indicate that sexual preference is a complex, heterogeneous phenotype.
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研究專屬網站:
Genetics of Sexual Behavior 
A website to communicate and share the results from the largest study on the genetics of sexual behavior
 

 (Nature對此研究之相關報導:No ‘gay gene’: Massive study homes in on genetic basis of human sexuality)

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