How do genes affect same-sex behavior? There's No Such Thing as a 'Gay Gene,' Massive Study Concludes.

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▼ Studies have indicated that same-sex orientation and behavior has a genetic basis and runs in families, yet specific genetic variants have not been isolated ( 1). Evidence that sexual orientation has a biological component could shape acceptance and legal protection: 4 to 10% of individuals report ever engaging in same-sex behavior in the United States, so this could affect a sizeable proportion of the population ( 2). On page 882 of this issue, Gannaet al.( 3) report the largest study to date, comprising almost half a million individuals in the United Kingdom and United States, identifying genetic variants associated with same-sex sexual behavior. They provide evidence that genetic variation accounts for a small fraction of same-sex sexual behavior and uncover a relationship to the regulation of the sex hormones testosterone and estrogen as well as sex-specific differences. They also reveal complexity of human sexuality.
The genetic basis of same-sex orientation and sexual behavior has evaded discovery, largely because of the challenges of using small and nonrepresentative cohorts. Initial evidence focused mostly on gay men, providing indirect and often speculative evidence of a relationship with fraternal birth order, prenatal exposure to sex hormones, neurodevelopmental traits, or maternal immunization to sex-specific proteins ( 4). Work in the 1990s isolated a relationship with the Xq28 region on the X chromosome ( 5, 6). Subsequent studies found similarity in the sexual orientation of identical twins, with genetics explaining 18% (for women) and 37% (for men), with the remainder accounted for by directly shared environments (such as family or school) and nonshared environments (such as legalization or norms regarding same-sex behavior) ( 7). Many of these studies could not be replicated, and although twin and family studies found a genetic basis, they could not isolate variants associated with same-sex orientation at specific genetic loci.
The study of Gannaet al.involved a genome-wide association study (GWAS), in which the genome is analyzed for statistically significant associations between single-nucleotide polymorphisms (SNPs) and a particular trait. SNPs are single-nucleotide base differences in DNA that allow the measurement of variation in a population. The approach of using a large cohort, sex-specific analyses, and complex measures of sexuality (for example, proportion of same-sex partners to total sexual partners, attraction, and identity) allowed the detection of genetic—and even sex-specific—variants that had evaded prior research.
Gannaet al.analyzed the association of ever having sex with a same-sex partner with SNPs in genomes from the UK Biobank (408,995 individuals) and from 23andMe (68,527 individuals from the United States), (▪ ▪ ▪)

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