Genome-wide association study of male sexual orientation

Alan R. Sanders*, Gary W. Beecham, Shengru Guo, Khytam Dawood, Gerulf Rieger, Judith A. Badner, Elliot S. Gershon, Ritesha S. Krishnappa, Alana B. Kolundzija, Jubao Duan, Jianxin Shi, Douglas F. Levinson, Bryan J. Mowry, Ann Olincy, Farooq Amin, C. Robert Cloninger, Dragan M. Svrakic, Jeremy M. Silverman, Nancy G. Buccola, William F. Byerley & 5 others Donald W. Black, Robert Freedman, Pablo V. Gejman, Michael Bailey, Eden R. Martin

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number16950
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Genome-Wide Association Study
Sexual Behavior
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 13
Thyroid Gland
Genes
Chromosomes, Human, Pair 14
X Chromosome Inactivation
Diencephalon
Chromosomes, Human, Pair 8
Twin Studies
Male Homosexuality
Graves Disease
Heterosexuality
Introns
Mothers
Genome
Sexual Minorities

ASJC Scopus subject areas

  • General

Cite this

Sanders, A. R., Beecham, G. W., Guo, S., Dawood, K., Rieger, G., Badner, J. A., ... Martin, E. R. (2017). Genome-wide association study of male sexual orientation. Scientific reports, 7(1), [16950]. https://doi.org/10.1038/s41598-017-15736-4
Sanders, Alan R. ; Beecham, Gary W. ; Guo, Shengru ; Dawood, Khytam ; Rieger, Gerulf ; Badner, Judith A. ; Gershon, Elliot S. ; Krishnappa, Ritesha S. ; Kolundzija, Alana B. ; Duan, Jubao ; Shi, Jianxin ; Levinson, Douglas F. ; Mowry, Bryan J. ; Olincy, Ann ; Amin, Farooq ; Cloninger, C. Robert ; Svrakic, Dragan M. ; Silverman, Jeremy M. ; Buccola, Nancy G. ; Byerley, William F. ; Black, Donald W. ; Freedman, Robert ; Gejman, Pablo V. ; Bailey, Michael ; Martin, Eden R. / Genome-wide association study of male sexual orientation. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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abstract = "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.",
author = "Sanders, {Alan R.} and Beecham, {Gary W.} and Shengru Guo and Khytam Dawood and Gerulf Rieger and Badner, {Judith A.} and Gershon, {Elliot S.} and Krishnappa, {Ritesha S.} and Kolundzija, {Alana B.} and Jubao Duan and Jianxin Shi and Levinson, {Douglas F.} and Mowry, {Bryan J.} and Ann Olincy and Farooq Amin and Cloninger, {C. Robert} and Svrakic, {Dragan M.} and Silverman, {Jeremy M.} and Buccola, {Nancy G.} and Byerley, {William F.} and Black, {Donald W.} and Robert Freedman and Gejman, {Pablo V.} and Michael Bailey and Martin, {Eden R.}",
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Sanders, AR, Beecham, GW, Guo, S, Dawood, K, Rieger, G, Badner, JA, Gershon, ES, Krishnappa, RS, Kolundzija, AB, Duan, J, Shi, J, Levinson, DF, Mowry, BJ, Olincy, A, Amin, F, Cloninger, CR, Svrakic, DM, Silverman, JM, Buccola, NG, Byerley, WF, Black, DW, Freedman, R, Gejman, PV, Bailey, M & Martin, ER 2017, 'Genome-wide association study of male sexual orientation', Scientific reports, vol. 7, no. 1, 16950. https://doi.org/10.1038/s41598-017-15736-4

Genome-wide association study of male sexual orientation. / Sanders, Alan R.; Beecham, Gary W.; Guo, Shengru; Dawood, Khytam; Rieger, Gerulf; Badner, Judith A.; Gershon, Elliot S.; Krishnappa, Ritesha S.; Kolundzija, Alana B.; Duan, Jubao; Shi, Jianxin; Levinson, Douglas F.; Mowry, Bryan J.; Olincy, Ann; Amin, Farooq; Cloninger, C. Robert; Svrakic, Dragan M.; Silverman, Jeremy M.; Buccola, Nancy G.; Byerley, William F.; Black, Donald W.; Freedman, Robert; Gejman, Pablo V.; Bailey, Michael; Martin, Eden R.

In: Scientific reports, Vol. 7, No. 1, 16950, 01.12.2017.

Research output: Contribution to journalArticle

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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, Michael

AU - Martin, Eden R.

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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Sanders AR, Beecham GW, Guo S, Dawood K, Rieger G, Badner JA et al. Genome-wide association study of male sexual orientation. Scientific reports. 2017 Dec 1;7(1). 16950. https://doi.org/10.1038/s41598-017-15736-4