TY - JOUR
T1 - Genome-wide association study of male sexual orientation
AU - Sanders, Alan R.
AU - Beecham, Gary W.
AU - Guo, Shengru
AU - Dawood, Khytam
AU - Rieger, Gerulf
AU - Badner, Judith A.
AU - Gershon, Elliot S.
AU - Krishnappa, Ritesha S.
AU - Kolundzija, Alana B.
AU - Duan, Jubao
AU - Shi, Jianxin
AU - Levinson, Douglas F.
AU - Mowry, Bryan J.
AU - Olincy, Ann
AU - Amin, Farooq
AU - Cloninger, C. Robert
AU - Svrakic, Dragan M.
AU - Silverman, Jeremy M.
AU - Buccola, Nancy G.
AU - Byerley, William F.
AU - Black, Donald W.
AU - Freedman, Robert
AU - Gejman, Pablo V.
AU - Bailey, J. Michael
AU - Martin, Eden R.
N1 - Funding Information:
This work was supported by NICHD: the Eunice Kennedy Shriver National Institute of Child Health and Human Development (A.R.S., grant no. R01HD041563 for the Affymetrix 5.0 genotyped sample and A.R.S. and E.R.M., grant no. R21HD080410 for various analyses), and by the Molecular Genetics of Schizophrenia (MGS) Collaboration for the Affymetrix 6.0 genotyped sample. The MGS Collaboration includes P.V.G., A.R.S., and J.D., in addition to the individuals in the MGS Collaboration group author list. MGS was mainly supported by R01MH059571, R01MH081800, and U01MH079469 (to P.V.G.), and other NIH grants for other MGS sites (R01MH067257 to N.G.B., R01MH059588 to B.J.M., R01MH059565 to R.F., R01MH059587 to F.A., R01MH060870 to W.F.B., R01MH059566 to D.W.B., R01MH059586 to J.M.S., R01MH061675 to D.F.L., R01MH060879 to C.R.C., U01MH046276 to C.R.C., and U01MH079470 to D.F.L). We thank the men for their participation, Timothy F. Murphy for his work on the community advisory board and study website, and Besiana Liti for technical assistance.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10-5, including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10-7) and 14 (p = 4.7 × 10-7). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10-3) for a SNP association previously reported (rs77013977, p = 7.1 × 10-8), with the combined analysis yielding p = 6.7 × 10-9, i.e., a genome-wide significant association.
AB - Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10-5, including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10-7) and 14 (p = 4.7 × 10-7). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10-3) for a SNP association previously reported (rs77013977, p = 7.1 × 10-8), with the combined analysis yielding p = 6.7 × 10-9, i.e., a genome-wide significant association.
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U2 - 10.1038/s41598-017-15736-4
DO - 10.1038/s41598-017-15736-4
M3 - Article
C2 - 29217827
AN - SCOPUS:85038086437
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 16950
ER -