Editing Biology and sexual orientation (section)

=== Genetic influences ===
Multiple genes have been found to play a role in sexual orientation. Scientists caution that many people misconstrue the meanings of ''genetic'' and ''environmental''.<ref name="Bailey_2016"/> ''[[Environment and sexual orientation|Environmental influence]]'' does not automatically imply that the social environment influences or contributes to the development of sexual orientation. Hypotheses for the impact of the post-natal social environment on sexual orientation are weak, especially for males.<ref name="Bailey_2016"/> There is, however, a vast non-social environment that is non-genetic, such as [[prenatal development]], which remains poorly understood.<ref name="Bailey_2016"/>{{rp|76}}

====Twin studies====
Twin studies are one method of testing genetic and environmental influences, although they cannot reveal what kind of environmental influence this may include (social or non-social).{{Sfn|Bailey|2003|p=110–111}} Identical or monozygotic twins share their genes, while fraternal or dizygotic twins are only as genetically similar as any other sibling pair. When twins both share a trait, they are ''concordant'' for this trait; and when they differ they are [[Discordant Twins|''discordant'']]. If identical twins have a higher rate of concordance for a trait than fraternal twins, it indicates that genes may contribute to the trait.<ref name="Bailey_2016" />{{rp|74–76}}

The 2016 Bailey et al. meta-analysis of all twin studies on sexual orientation found that the [[median]] concordance for homosexual or non-heterosexual orientation in twins in unbiased probability samples is 24% for monozygotic identical twins, and 15% for dizygotic twins.<ref name="Bailey_2016" />{{rp|74–76}} According to Rice et al. the identical twin concordance for homosexuality is similar to identical twin concordance for two other traits influenced by prenatal androgens: [[cryptorchidism]] and [[hypospadias]] (feminized male gonads) which have an identical twin concordance around 25%, despite twins sharing genes and prenatal environments.<ref name=":4">{{Cite journal |last1=Rice |first1=William R. |last2=Friberg |first2=Urban |last3=Gavrilets |first3=Sergey |date=2012 |title=Homosexuality as a Consequence of Epigenetically Canalized Sexual Development |url=http://scottbarrykaufman.com/wp-content/uploads/2012/12/Rice-et-al.-2012.pdf |journal=The Quarterly Review of Biology |volume=87 |issue=4 |pages=343–368 |doi=10.1086/668167 |pmid=23397798 |issn=0033-5770}}</ref>{{rp|356}}[[File:Gary_and_Larry_Lane_photo.jpg|alt=|thumb|250x250px|Identical twin studies are a useful mechanism for assessing the role of genes and environment.]]Twin studies have also found that among twins with differing sexual orientations, homosexual twins were significantly more [[gender nonconforming]] than their heterosexual co-twin, and that this was noticeable from a young age.{{Sfn|Bailey|2003|p=110–111}} Bailey states:
{{Quote|text=What kind of environmental factor can cause genetically identical twins reared in the same family from birth—often dressed alike and given the same toys—to differ in their sexual orientations? It is a fascinating question that we haven’t begun to answer well. One hint comes from the childhood behavior findings. When identical twins differed in their sexual orientation, the gay one tended to recall being much more feminine than the straight one. This means that the environmental factors that cause the twin differences are there early on, by childhood. Based on other things we know, such as studies of children with cloacal exstrophy, I suspect that these factors operate in the womb.{{Sfn|Bailey|2003|p=110–111}}}}
Identical twins reared apart from birth are another method of studying the origin of psychological traits. Unfortunately, such twin pairs are rare. Three sets of male twin pairs exist in the literature. In the first pair found by Thomas Bouchard, both male twins reared apart from birth were homosexual. In a second pair found by Whitham, both males were also homosexual. In the third pair found by Bouchard, the male twins were neither definitively concordant nor discordant, as both had relations with males and females, thus this pair may be concordant for bisexuality. Among the female twin pairs; four female twin pairs were all discordant, although the small number of cases prevent any strong conclusions.{{Sfn|LeVay|2017|p=89–90}}

According to William Rice and colleagues, the concordance of homosexuality among twins raises the possibility that homosexuality is not caused by genes nor atypical levels of hormones, but an epigenetic mechanism controlling how sensitive fetuses are to prenatal hormones.<ref name=":4" /><ref>{{Cite journal |last=Tasos |first=Emmanouil |date=2022 |title=To What Extent are Prenatal Androgens Involved in the Development of Male Homosexuality in Humans? |url=https://www.researchgate.net/publication/352125966 |journal=Journal of Homosexuality |language=en |volume=69 |issue=11 |pages=1928–1963 |doi=10.1080/00918369.2021.1933792 |pmid=34080960 |issn=0091-8369 |via=ResearchGate}}</ref>{{Rp|page=22}}

====Chromosome linkage studies====
{{gay gene}}
Chromosome linkage studies of sexual orientation have indicated the presence of multiple contributing genetic factors throughout the genome. In 1993, [[Dean Hamer]] and colleagues published findings from a linkage analysis of a sample of 76 gay brothers and their families.<ref>{{cite journal | vauthors = Hamer DH, Hu S, Magnuson VL, Hu N, Pattatucci AM | title = A linkage between DNA markers on the X chromosome and male sexual orientation | journal = Science | volume = 261 | issue = 5119 | pages = 321–7 | date = July 1993 | pmid = 8332896 | doi = 10.1126/science.8332896 | url = https://zenodo.org/record/1231257 | bibcode = 1993Sci...261..321H }}</ref> Hamer et al. found that the gay men had more gay male uncles and cousins on the maternal side of the family than on the paternal side. Gay brothers who showed this maternal pedigree were then tested for X chromosome linkage, using twenty-two markers on the X chromosome to test for similar alleles. In another finding, thirty-three of the forty sibling pairs tested were found to have similar alleles in the distal region of [[Xq28]], which was significantly higher than the expected rates of 50% for fraternal brothers. This was popularly dubbed the "'''gay gene'''" in the media, causing significant controversy. In 1998, Sanders et al.{{citation needed|date=June 2022}} reported on their similar study, in which they found that 13% of uncles of gay brothers on the maternal side were homosexual, compared with 6% on the paternal side.<ref name="Wilson_2008">{{cite book | vauthors = Wilson G, Rahman Q  |title=Born Gay: The Psychobiology of Sex Orientation |date=2008 |publisher=Peter Owen Publishers |isbn=9780720613094 |edition= 2nd |language=en}}</ref>

A later analysis by Hu et al. replicated and refined the earlier findings. This study revealed that 67% of gay brothers in a new saturated sample shared a marker on the X chromosome at Xq28.<ref name="Hu_1995">{{cite journal | vauthors = Hu S, Pattatucci AM, Patterson C, Li L, Fulker DW, Cherny SS, Kruglyak L, Hamer DH | display-authors = 6 | title = Linkage between sexual orientation and chromosome Xq28 in males but not in females | journal = Nature Genetics | volume = 11 | issue = 3 | pages = 248–56 | date = November 1995 | pmid = 7581447 | doi = 10.1038/ng1195-248 | url = https://zenodo.org/record/1233407 | type = Submitted manuscript | s2cid = 721490 }}</ref> Two other studies (Bailey et al., 1999; McKnight and Malcolm, 2000) failed to find a preponderance of gay relatives in the maternal line of homosexual men.<ref name="Wilson_2008"/> One study by Rice et al. in 1999 failed to replicate the Xq28 linkage results.<ref>{{cite journal | vauthors = Vilain E | title = Genetics of sexual development | journal = Annual Review of Sex Research | volume = 11 | pages = 1–25 | year = 2000 | doi = 10.1080/10532528.2000.10559783 | pmid = 11351829 }}</ref> Meta-analysis of all available linkage data indicates a significant link to Xq28, but also indicates that additional genes must be present to account for the full heritability of sexual orientation.<ref name="Hamer_1999">{{cite journal | vauthors = Hamer DH, Rice G, Risch N, Ebers G |title=Genetics and Male Sexual Orientation |journal=Science |date=1999 |volume=285 |issue=5429 |page=803 |doi=10.1126/science.285.5429.803a |doi-access=free}}</ref>

Mustanski et al. (2005) performed a full-genome scan (instead of just an X chromosome scan) on individuals and families previously reported on in Hamer et al. (1993) and Hu et al. (1995), as well as additional new subjects. In the full sample they did not find linkage to Xq28.<ref>{{cite journal | vauthors = Mustanski BS, Dupree MG, Nievergelt CM, Bocklandt S, Schork NJ, Hamer DH | title = A genomewide scan of male sexual orientation | journal = Human Genetics | volume = 116 | issue = 4 | pages = 272–8 | date = March 2005 | pmid = 15645181 | doi = 10.1007/s00439-004-1241-4 | url = http://mypage.iu.edu/~bmustans/Mustanski_etal_2005.pdf | url-status = dead | s2cid = 206989147 | archive-url = https://web.archive.org/web/20050415233637/http://mypage.iu.edu/~bmustans/Mustanski_etal_2005.pdf | archive-date = 2005-04-15 }}</ref>

Results from the first large, comprehensive multi-center genetic linkage study of male sexual orientation were reported by an independent group of researchers at the American Society of Human Genetics in 2012.<ref name="Sanders_2014">{{cite journal | vauthors = Sanders AR, Martin ER, Beecham GW, Guo S, Dawood K, Rieger G, Badner JA, Gershon ES, Krishnappa RS, Kolundzija AB, Duan J, Gejman PV, Bailey JM | display-authors = 6 | title = Genome-wide scan demonstrates significant linkage for male sexual orientation | journal = Psychological Medicine | volume = 45 | issue = 7 | pages = 1379–88 | date = May 2015 | pmid = 25399360 | doi = 10.1017/S0033291714002451 | s2cid = 4027333 }}</ref> The study population included 409 independent pairs of gay brothers, who were analyzed with over 300,000 [[single-nucleotide polymorphism]] markers. The data strongly replicated Hamer's Xq28 findings as determined by both two-point and multipoint (MERLIN) LOD score mapping. Significant linkage was also detected in the pericentromeric region of chromosome 8, overlapping with one of the regions detected in the Hamer lab's previous genomewide study. The authors concluded that "our findings, taken in context with previous work, suggest that genetic variation in each of these regions contributes to development of the important psychological trait of male sexual orientation". Female sexual orientation does not seem to be linked to Xq28,<ref name="Hu_1995"/><ref name="Ngun_2014">{{cite book | vauthors = Ngun TC, Vilain E |title=The Biological Basis of Human Sexual Orientation: Is There a Role for Epigenetics? |chapter=The Biological Basis of Human Sexual Orientation |date=2014 |volume=86 |pages=167–84 |doi=10.1016/B978-0-12-800222-3.00008-5 |pmid=25172350 |url=http://gaystudies.genetics.ucla.edu/UCLA%20Twin%20Sexual%20Orientation%20Study/Read%20More_files/Ngun.pdf |access-date=20 March 2016 |issn=0065-2660 |series=Advances in Genetics |isbn=9780128002223 |archive-url=https://web.archive.org/web/20160331225443/http://gaystudies.genetics.ucla.edu/UCLA%20Twin%20Sexual%20Orientation%20Study/Read%20More_files/Ngun.pdf |archive-date=2016-03-31 |url-status=dead}}</ref> though it does appear moderately heritable.<ref name="Sanders_2014"/>

In addition to [[allosome|sex chromosomal]] contribution, a potential [[autosomal]] genetic contribution to the development of homosexual orientation has also been suggested. In a study population composed of more than 7000 participants, Ellis et al. (2008) found a statistically significant difference in the frequency of blood type A between homosexuals and heterosexuals. They also found that "unusually high" proportions of homosexual males and homosexual females were [[Rh factor|Rh negative]] in comparison to heterosexuals. As both blood type and Rh factor are genetically inherited traits controlled by [[alleles]] located on chromosome 9 and chromosome 1 respectively, the study indicates a potential link between genes on autosomes and homosexuality.<ref>{{cite journal | vauthors = Ellis L, Ficek C, Burke D, Das S | title = Eye color, hair color, blood type, and the rhesus factor: exploring possible genetic links to sexual orientation | url = https://archive.org/details/sim_archives-of-sexual-behavior_2008-02_37_1/page/145 | journal = Archives of Sexual Behavior | volume = 37 | issue = 1 | pages = 145–9 | date = February 2008 | pmid = 18074215 | doi = 10.1007/s10508-007-9274-0 | s2cid = 8303331 }}</ref><ref name="AnHomGenetics">{{cite book | vauthors = Poiani A |title=Animal Homosexuality: A Biosocial Perspective |date=2010 |publisher=Cambridge University Press |isbn=978-1139490382 |pages=55–96|url=https://books.google.com/books?id=EftT_1bsPOAC}}</ref>

The biology of sexual orientation has been studied in detail in several animal model systems. In the common fruit fly ''[[Drosophila melanogaster]]'', the complete pathway of sexual differentiation of the brain and the behaviors it controls is well established in both males and females, providing a concise model of biologically controlled courtship.<ref>{{cite journal | vauthors = Pavlou HJ, Goodwin SF | title = Courtship behavior in Drosophila melanogaster: towards a 'courtship connectome' | journal = Current Opinion in Neurobiology | volume = 23 | issue = 1 | pages = 76–83 | date = February 2013 | pmid = 23021897 | pmc = 3563961 | doi = 10.1016/j.conb.2012.09.002 }}</ref> In mammals, a group of geneticists at the Korea Advanced Institute of Science and Technology bred female mice specifically lacking a particular gene related to sexual behavior. Without the gene, the mice exhibited masculine sexual behavior and attraction toward urine of other female mice. Those mice who retained the gene fucose mutarotase (FucM) were attracted to male mice.<ref>{{cite journal | vauthors = Park D, Choi D, Lee J, Lim DS, Park C | title = Male-like sexual behavior of female mouse lacking fucose mutarotase | journal = BMC Genetics | volume = 11 | pages = 62 | date = July 2010 | pmid = 20609214 | pmc = 2912782 | doi = 10.1186/1471-2156-11-62 | doi-access = free }}</ref>

In interviews to the press, researchers have pointed that the evidence of genetic influences should not be equated with genetic determinism. According to Dean Hamer and Michael Bailey, genetic aspects are only one of the multiple causes of homosexuality.<ref>{{cite web |url=https://www.independent.co.uk/news/the-gay-gene-is-back-on-the-scene-1536770.html |title=The 'gay gene' is back on the scene | vauthors = Connor S |date=31 October 1995 |website=[[The Independent]]}}</ref><ref>{{cite web |url=https://www.telegraph.co.uk/science/science-news/10637532/Being-homosexual-is-only-partly-due-to-gay-gene-research-finds.html |archive-url=https://web.archive.org/web/20140214023529/http://www.telegraph.co.uk/science/science-news/10637532/Being-homosexual-is-only-partly-due-to-gay-gene-research-finds.html |url-status=dead |archive-date=February 14, 2014 |title=Being homosexual is only partly due to gay gene, research finds | vauthors = Knapton S |date=13 February 2014 |website=The Telegraph |publisher=[[Telegraph Media Group]]}}</ref>

In 2017, ''[[Scientific Reports]]'' published an article with a [[genome wide association study]] on male sexual orientation. The research consisted of 1,077 homosexual men and 1,231 heterosexual men. A gene named ''[[SLITRK6]]'' on [[chromosome 13]] was identified.<ref name="Sanders_2017">{{cite journal | vauthors = Sanders AR, Beecham GW, Guo S, Dawood K, Rieger G, Badner JA, Gershon ES, Krishnappa RS, Kolundzija AB, Duan J, Gejman PV, Bailey JM, Martin ER | display-authors = 6 | title = Genome-Wide Association Study of Male Sexual Orientation | language = En | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 16950 | date = December 2017 | pmid = 29217827 | pmc = 5721098 | doi = 10.1038/s41598-017-15736-4 | bibcode = 2017NatSR...716950S }}</ref> The research supports another study which had been done by the neuroscientist [[Simon LeVay]]. LeVay's research suggested that the [[hypothalamus]] of gay men is different from straight men.<ref name="LeVay_1991"/> The SLITRK6 is active in the mid-brain where the hypothalamus is. The researchers found that the [[Thyrotropin receptor|thyroid stimulating hormone receptor]] (TSHR) on chromosome 14 shows sequence differences between gay and straight men.<ref name="Sanders_2017" /> [[Graves' disease]] is associated with TSHR abnormalities, with previous research indicating that Graves' disease is more common in gay men than in straight men.<ref name=nielsen2013>{{cite journal | vauthors = Frisch M, Nielsen NM, Pedersen BV | title = Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008 | journal = European Journal of Epidemiology | volume = 29 | issue = 1 | pages = 63–71 | date = January 2014 | pmid = 24306355 | doi = 10.1007/s10654-013-9869-9 | s2cid = 11819672 }}</ref> Research indicated that gay people have lower body weight than straight people. It had been suggested that the overactive TSHR hormone lowered body weight in gay people, though this remains unproven.<ref>{{cite journal | vauthors = Deputy NP, Boehmer U | title = Determinants of body weight among men of different sexual orientation | journal = Preventive Medicine | volume = 51 | issue = 2 | pages = 129–31 | date = August 2010 | pmid = 20510272 | doi = 10.1016/j.ypmed.2010.05.010 }}</ref><ref>{{cite journal | vauthors = Blanchard R, Bogaert AF | title = Biodemographic comparisons of homosexual and heterosexual men in the Kinsey Interview Data | url = https://archive.org/details/sim_archives-of-sexual-behavior_1996-12_25_6/page/551 | journal = Archives of Sexual Behavior | volume = 25 | issue = 6 | pages = 551–79 | date = December 1996 | pmid = 8931880 | doi = 10.1007/BF02437839 | s2cid = 23951518 }}</ref>

In 2018, Ganna et al. performed another [[genome-wide association study]] on sexual orientation of men and women with data from 26,890 people who had at least one same-sex partner and 450,939 controls. The data in the study was meta-analyzed and obtained from the [[UK Biobank]] study and [[23andMe]]. The researchers identified four variants more common in people who reported at least one same-sex experience on chromosomes 7, 11, 12, and 15. The variants on chromosomes 11 and 15 were specific to men, with the variant on chromosome 11 located in an olfactory gene and the variant on chromosome 15 having previously been linked to male-pattern baldness. The four variants were also correlated with mood and mental health disorders; major depressive disorder and schizophrenia in men and women, and bipolar disorder in women. However, none of the four variants could reliably predict sexual orientation.<ref>{{cite web|url=https://www.science.org/content/article/giant-study-links-dna-variants-same-sex-behavior|title=Giant study links DNA variants to same-sex behavior| vauthors = Price M |date=2018-10-19|website=Science | publisher = AAAS |language=en|access-date=2019-01-21}}</ref>

In August 2019, a genome-wide association study of 493,001 individuals concluded that hundreds or thousands of genetic variants underlie homosexual behavior in both sexes, with 5 variants in particular being significantly associated. Some of these variants had sex-specific effects, and two of these variants suggested links to biological pathways that involve [[sex hormone]] regulation and [[olfaction]]. All the variants together captured between 8 and 25% of the variation in individual differences in homosexual behavior. These genes partly overlap with those for several other traits, including openness to experience and risk-taking behavior. Additional analyses suggested that sexual behavior, attraction, identity, and fantasies are influenced by a similar set of genetic variants. They also found that the genetic effects that differentiate heterosexual from homosexual 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 heterosexual to homosexual preference, as suggested by the [[Kinsey scale]].<ref name="Science 2019">{{cite journal | vauthors = Ganna A, Verweij KJ, Nivard MG, Maier R, Wedow R, Busch AS, Abdellaoui A, Guo S, Sathirapongsasuti JF, Lichtenstein P, Lundström S, Långström N, Auton A, Harris KM, Beecham GW, Martin ER, Sanders AR, Perry JR, Neale BM, Zietsch BP | display-authors = 6 | title = Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior | journal = Science | volume = 365 | issue = 6456 | pages = eaat7693 | date = August 2019 | pmid = 31467194 | pmc = 7082777 | doi = 10.1126/science.aat7693 }}</ref><ref>{{cite web |title=Genetics of Sexual Behavior |url=https://geneticsexbehavior.info/what-we-found/ |website=Genetics of Sexual Behavior |publisher=geneticsexbehavior.info |access-date=30 August 2019 |date=28 February 2018}}</ref>

In October 2021, another research paper reported that genetic factors influence the development of same-sex sexual behavior. A two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in [[Han Chinese]] populations identified two genetic loci (FMR1NB and ZNF536) showing consistent association with male sexual orientation.<ref name="Hu_2021">{{cite journal | vauthors = Hu SH, Li HM, Yu H, Liu Y, Liu CX, Zuo XB, Lu J, Jiang JJ, Xi CX, Huang BC, Xu HJ, Hu JB, Lai JB, Huang ML, Liu JN, Xu DG, Guo XC, Wu W, Wu X, Jiang L, Li M, Zhang GP, Huang JW, Wei N, Lv W, Duan JF, Qi HL, Hu CC, Chen JK, Zhou WH, Xu WJ, Liu CF, Liang HY, Du J, Zheng SF, Lu QL, Zheng L, Hu XW, Chen FX, Chen P, Zhu B, Xu LJ, Ni ZM, Fang YZ, Yang ZK, Shan XR, Zheng ED, Zhang F, Zhou QQ, Rao Y, Swaab D, Yue WH, Xu Y | display-authors = 6 | title = Discovery of new genetic loci for male sexual orientation in Han population | journal = Cell Discovery | volume = 7 | issue = 1 | pages = 103 | date = October 2021 | pmid = 34719679 | pmc = 8558329 | doi = 10.1038/s41421-021-00341-7 }}</ref>