Evolution has always shaped and adapted organisms to their environments and available resources, using genes as the carriers of information across generations. The only direction that selective pressure can impose on individuals, is towards reproduction, in other words selecting adaptations to ensure the survival of the next generation.

But what happens to those traits that seem to defeat this purpose? 

The question if homosexuality has genetic origins, has always fascinated me because of how common this trait is both across and within species. In this post i focused mainly on the genetics behind homosexuality in humans.

Homosexual behavior in families

Looking for genetic markers or genes that are responsible for a complex trait like sexual orientation is very challenging; when I was looking for information on the topic I found that studies often focus on two different aspects, (I) the heritability of the trait and (II) the specific regions on the genome that correlates significantly with homosexual behavior.

If homosexuality was completely independent of genetics, the probability of having the trait should be the same for everyone regardless of their genetic background or genealogical tree. This is the basic hypothesis in identical twins studies, in other words: is there a significantly increased chance for an individual to be homosexual, given that the homozygous twin express the behavior?

Kocharyan G. [2] reviewed different studies on the topic, investigating the significance of twin studies results, their implications on the heritability of homosexuality, and the effects of other environmental factors. To measure the effect of genetics, the studies use a percentage of concordance, defined as the fraction of twin pairs that show the same sexual orientation, on the total number of pairs.

The data seems to vary a lot, probably due to differences in the panel selection, but the concordance for homozygous twins in regards to homosexuality varies between 20 and 50%, with some differences found between the two sexes. As a comparison, the concordance for siblings (brothers and sisters) goes only from 10 to 20%.  An interesting point raised in the article is that distinguishing between the effects of genetics and the environment in the development of sexual orientation is impossible since the more similar two siblings are, the more similar they have been brought up. This could explain the differences in concordance found between dizygous twins and siblings: since both the groups received 50% of their genes from each parent independently, they should have the same concordance for homosexuality; but the concordance for non-identical twins is higher. This can be because two heterozygous twins, even with different genetic materials, have been exposed to similar events at around the same age, and they have been treated similarly by the parents in about the same environment.

The environment seems to play a crucial role in determining the homosexuality trait, with the genetic contribution ranging only from 15 to 20%, and the environment accounting for the remaining part. It looks like genes have a minor role in the determination of homosexuality, accounting (maybe) only for a predisposition.

But if differences are in fact present, however minor they may be, finding which are the genetic mutations responsible for this trait is the next logical step.


Looking for the "gay gene"

The experiments that try to associate a particular trait to a specific genomic region are called phenotypic associations, and they usually involve Genome-Wide Association Studies (GWAS). With this technic,  the DNA is first extracted from the subjects, and the genome sequence is obtained, from here, the researchers look for specific mutations, often at the single nucleotide level (SNPs). Afterward, a statistical analysis is carried out to associate SNPs with the trait/disease of interest, and a probability threshold on the correlation (p-values in the order of the 10^-8) is applied to find highly correlated SNPs with the trait.

Ganna A. et al. [4] present a big GWAS study conducted on a big sample of 500,000 genomes, found in the UK Biobank containing the genomes of residents aged between 40 and 70 (other 3 smaller datasets were used as a comparison). The researchers tried first to understand if the heritability of homosexuality was clustered in families, and found that closely related individuals (cousins or closer) were in fact more likely to show the same sexual orientation, finding what they called a "broad-sense heritability" value of 32% (percentage of variability in homosexuality explained by genetics), a result which is very close to the estimates of twin studies.

Figure 1: Manhattan plot for a GWAS of same-sex sexual behavior. In the legend are reported the SNPs which are significantly associated with homosexual behavior in both, or just one of the sexes.


Interestingly, the researchers found 5 different SNPs (Fig1) that correlated with homosexual behavior, 2 of which were common in both sexes, 2 in males and 1 in females, they also explain how difficult it seems to find across-sexes correlation for homosexuality, implying that the genetic origins for homosexuality could be different between male and females. 

Integrating these data with other studies on phenotypes and expression of quantitative trait loci (regions associated with gene expression), the researchers found the functions associated in these genomic regions, for example:

  • rs34730029 (males): is associated with a variant of OR5A1, a gene responsible for the sensibility to certain scents, and contained in a bigger region that contains a lot of genes encoding for olfactory receptors.
  • rs28371400 (males): plays a role in hormone regulation. The allele correlated in the study with homosexual behavior, is also correlated with male hair loss pattern (in which hormones play a crucial role). Finally, they discovered that this gene is located upstream of another gene responsible for the development of gonads in mice, and involved in the male sex determination in humans.
Although a high statistical significance was found with these SNPs, the single polymorphisms didn't contribute that much to the development of same-sex attraction, for example, males that have the GT genotype for rs34730029, showed just a 0.4% increased prevalence of homosexuality, with the summed effect of the SNPs explaining only  8-25% of the variability in the dataset.

Another method to find interesting genomic regions is the linkage analysis, it's similar to GWAS in the sense that often looks for SNPs to associate with the trait, but it's more focused on the inheritability of the trait in the family. A study [3] found an interesting mutation (SNP rs760335) on chromosome 14 while looking for associations specific to homosexual behavior in men, but the likelihood score obtained failed to reach the genome-wide significance.


Conclusions

So far, the answer to the question of the genetic origin of homosexuality seems to be that some level of genetic influence/predisposition is, in fact, present, as shown by GWAS and linkage studies, although they were not able to point to a single "gay gene" responsible for the trait. The variation of the trait in the population given by genetics seems to be so low that environmental factors can easily overcome them, in fact, none of the genetic variations found in GWAS can be used as a good estimator for the sexual orientation of an individual.

It's important to note that two aspects of these studies can have a huge impact on the results if not treated correctly, one is the panel selection: the sexual orientation of individuals mustn't play a role in their decision to partecipate in the experiment. Secondly, in many studies, to obtain an easy variable to work with (and some level of significance), any individual who had a homosexual experience is categorized as homosexual. This choice, as stated by the same authors is a simplification that doesn't account for the fluidity of human sexual orientation. 

Finally, I had to cut short on a few aspects that these studies address, like the correlation between homosexuality and other heritable predispositions, the effect of the social stigma on homosexuality on the development of distress and other mental diseases, and what are the "environmental" variables that must be the main actors in the development of this trait. 

I would also like to explore in another post the different evolutionary hypotheses for homosexuality in humans and other mammals.

References:

  1. McHenry, S. E. (2022). “Gay Is Good”: History of Homosexuality in the DSM and Modern Psychiatry. American Journal of Psychiatry Residents' Journal.: On the history of homosexuality in the "Manual of Mental Disorders"
  2. Коcharyan, G. (2019). On The Influence of Genetic Factors on the Formation of Homosexuality by Data of Twin Studies. Psychological Counseling and Psychotherapy, (11), 67-73. 
  3. Ramagopalan, S. V., Dyment, D. A., Handunnetthi, L., Rice, G. P., & Ebers, G. C. (2010). A genome-wide scan of male sexual orientation. Journal of Human Genetics, 55(2), 131-132.
  4. Ganna, A., Verweij, K. J., Nivard, M. G., Maier, R., Wedow, R., Busch, A. S., ... & Zietsch, B. P. (2019). Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior. Science, 365(6456), eaat7693.
  5. Poiani, A. (2010). Animal Homosexuality in an evolutionary perspective. Animal Homosexuality: A Biosocial Perspective, 1-28.
  6. Poiani, A. (2010). Animal homosexuality: A biosocial perspective. Cambridge University Press.