Article : Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior
  • 1
  • Auteurs
    Andrea Ganna, Karin J. H. Verweij, Michel G. Nivard, Robert Maier, Robbee Wedow, Alexander S. Busch, Abdel Abdellaoui, Shengru Guo, J. Fah Sathirapongsasuti, Paul Lichtenstein, Sebastian Lundström, Niklas Långström, Adam Auton, Kathleen Mullan Harris, Gary W. Beecham, Eden R. Martin, Alan R. Sanders, John R. B. Perry, Benjamin M. Neale, Brendan P. Zietsch
  • Année de publication
    2019
  • Journal
    Science
  • Abstract (dans sa langue originale)

    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.

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