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GWAS Suggests Same-Sex Sexual Behavior Is Polygenic, Complex

NEW YORK – Results from a large genome-wide association study suggest that same-sex sexual behaviors stem from complex interactions between common genetic variants and environmental factors.

"We couldn't find any strong effect on chromosome X as was previously reported in the literature," co-first author Andrea Ganna said during a press briefing with reporters this week. "Sexual behavior is instead very polygenic, meaning there are a lot of variants that contribute to this trait."

Ganna was affiliated with Massachusetts General Hospital (MGH), the Broad Institute, and Karolinska Institute when the research was performed. He recently accepted a position as EMBL group leader at the Institute for Molecular Medicine Finland.

He and his colleagues were quick to point out that the new GWAS findings only reveal common genetic variants coinciding with participants' history of self-reported same-sex behaviors, and do not speak to participants' sexual identity.

In a statement provided by the LGBTQ media advocacy organization GLAAD, Zeke Stokes, GLAAD's chief programs officer, said the study "provides even more evidence that being gay or lesbian is a natural part of human life, a conclusion that has been drawn by researchers and scientists time and again."

The international team's GWAS, reported online today in Science, included individuals who reported having at least one same-sex sexual experience, though follow-up analyses looked at the proportion of same-sex partnerships in the participants' pasts and considered the degree of overlap between SNPs contributing to this behavior in men and women.

The authors noted that genetic variants that were associated with same-sex sexual behavior "only partially overlapped between males and females and do not allow meaningful prediction of an individual's sexual behavior."

Likewise, the researchers did not see any clear continuum when it came to genetic factors found in individuals with a higher or lower ratio of same-sex partners relative to partners overall in their histories, pointing to the complexity of sexual behavior.

"This study … provides the clearest links yet into the genetic underpinnings of same-sex sexual behavior — it highlights both the importance of the genetics as well as the complexity of the genetics," co-senior author Benjamin Neale, an analytic and translational genetics, population genetics, and psychiatric genetics researcher affiliated with MGH and the Broad Institute, told reporters. "But genetics is not the whole story. [The research] also underscores an important role for the environment in shaping human sexual behavior."

"This is not the first study exploring the genetics of same-sex behavior. But the previous studies were small and underpowered," Ganna told reporters, adding that "results of those studies were mostly not replicable."

Studies in families and twins suggest that there is a genetic component to same-sex sexual behavior, the team noted, and anywhere from 2 percent to 10 percent of individuals in societies from around the world say they have had same-sex sexual experiences.

To explore common genetic contributors to this partially heritable behavior, the researchers brought together genotyping profiles for 477,522 individuals from five cohorts, including UK Biobank project participants and research-consented 23andMe consumers. More than 26,827 participants reported past same-sex sexual behavior, though the proportion varied by cohort and with participants' age.

The team's search highlighted two loci on chromosomes 12 and 7 that had genome-wide significant associations with same-sex sexual behavior. Two more loci — falling on chromosomes 15 and 11 — were linked to the behavior in males, while a chromosome 4 locus turned up in women.

SNPs at two of the five loci reached genome-wide significance after a replication meta-analysis in 15,156 individuals, though the effect size of those variants remained small, the researchers reported. Together, though, common SNPs appeared to explain some 8 percent to 25 percent of the variation in self-reported same-sex sexual behavior.

The team did not see tissue or cell type enrichment for these SNPs, though a subsequent pathway analysis pointed to possible biological overlap with traits ranging from cannabis use, openness to experience, or number of overall sex partners to mental health conditions such as bipolar disorder, particularly in female participants. In males, associated SNPs fell at loci previously implicated in sense of smell and hormone regulation, respectively.

Even so, the authors cautioned against overinterpreting such correlations, which may not yield any causal relationships.

"Our findings provide insights into the biological underpinnings of same-sex sexual behavior but also underscore the importance of resisting simplistic conclusions — because the behavioral phenotypes are complex, because our genetic insights are rudimentary, and because there is a long history of misusing genetic results for social purposes," the authors concluded.

In a related editorial, University of Oxford sociology researcher Melinda Mills also pointed to the need for additional research to "investigate how genetic predispositions are altered by environmental factors, with this study highlighting the need for a multidisciplinary sociogenomic approach."

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