. 2019 Aug 30;365(6456):eaat7693.

doi: 10.1126/science.aat7693.

Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

Andrea Ganna^#^{1

2

3

4}, Karin J H Verweij^#⁵, Michel G Nivard⁶, Robert Maier^{1

2

3}, Robbee Wedow^{1

3

7

8

9

10

11}, Alexander S Busch^{12

13

14}, Abdel Abdellaoui⁵, Shengru Guo¹⁵, J Fah Sathirapongsasuti¹⁶; 23andMe Research Team; Paul Lichtenstein⁴, Sebastian Lundström¹⁷, Niklas Långström⁴, Adam Auton¹⁶, Kathleen Mullan Harris^{18

19}, Gary W Beecham¹⁵, Eden R Martin¹⁵, Alan R Sanders^{20

21}, John R B Perry^#¹², Benjamin M Neale^#^{1

2

3}, Brendan P Zietsch^#²²

Affiliations

¹ Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
² Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Psychiatry, Amsterdam University Medical Centers (UMC), location AMC, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, Netherlands.
⁶ Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT, Amsterdam, Netherlands.
⁷ Department of Sociology, Harvard University, Cambridge, MA 02138, USA.
⁸ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
⁹ Department of Sociology, University of Colorado, Boulder, CO 80309-0483, USA.
¹⁰ Health and Society Program and Population Program, Institute of Behavioral Science, University of Colorado, Boulder, CO 80309-0483, USA.
¹¹ Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309-0483, USA.
¹² Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
¹³ Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹⁴ International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark.
¹⁵ Department of Human Genetics, University of Miami, Miami, FL 33136, USA.
¹⁶ 23andMe, Mountain View, CA 94041, USA.
¹⁷ Centre for Ethics, Law and Mental Health, Gillberg Neuropsychiatry Centre, University of Gothenburg, Sweden.
¹⁸ Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
¹⁹ Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
²⁰ Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, IL 60201, USA.
²¹ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA.
²² Centre for Psychology and Evolution, School of Psychology, University of Queensland, St. Lucia, Brisbane QLD 4072, Australia. zietsch@psy.uq.edu.au.

^# Contributed equally.

PMID: 31467194
PMCID: PMC7082777
DOI: 10.1126/science.aat7693

Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

Andrea Ganna et al. Science. 2019.

. 2019 Aug 30;365(6456):eaat7693.

doi: 10.1126/science.aat7693.

Authors

Affiliations

¹ Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
² Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Psychiatry, Amsterdam University Medical Centers (UMC), location AMC, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, Netherlands.
⁶ Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT, Amsterdam, Netherlands.
⁷ Department of Sociology, Harvard University, Cambridge, MA 02138, USA.
⁸ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
⁹ Department of Sociology, University of Colorado, Boulder, CO 80309-0483, USA.
¹⁰ Health and Society Program and Population Program, Institute of Behavioral Science, University of Colorado, Boulder, CO 80309-0483, USA.
¹¹ Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309-0483, USA.
¹² Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
¹³ Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹⁴ International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark.
¹⁵ Department of Human Genetics, University of Miami, Miami, FL 33136, USA.
¹⁶ 23andMe, Mountain View, CA 94041, USA.
¹⁷ Centre for Ethics, Law and Mental Health, Gillberg Neuropsychiatry Centre, University of Gothenburg, Sweden.
¹⁸ Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
¹⁹ Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
²⁰ Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, IL 60201, USA.
²¹ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA.
²² Centre for Psychology and Evolution, School of Psychology, University of Queensland, St. Lucia, Brisbane QLD 4072, Australia. zietsch@psy.uq.edu.au.

^# Contributed equally.

PMID: 31467194
PMCID: PMC7082777
DOI: 10.1126/science.aat7693

Abstract

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.

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Figures

**Fig. 1.. Descriptive statistics regarding same-sex sexual behavior in the UK Biobank.**
(A)The percentage of participants in the UK Biobank who reported having had at least one same-sex sexual partner (y axis) increased with participants’ year of birth (x axis). (B) Among participants reporting at least one same-sex partner, those with a greater proportion of same-sex partners (x axis) have a larger reproductive disadvantage (lower birth-year adjusted number of children) (y axis). Vertical bars represent 95% CIs.

**Fig. 2.. Manhattan plot for a GWAS of same-sex sexual behavior.**
Diamonds (red) represent genome-wide significant signals from analysis of males and females combined, and triangles represent genome-wide significant signals that are female (pointing up, blue) or male (pointing down, green) specific.

**Fig. 3.. SNP-based versus family-based heritability estimates for same-sex sexual behavior compared with a variety of other traits.**
Heritability, h²; same-sex sexual behavior, red dot; other traits, gray dots. The estimates for all traits are provided in table S23. Horizontal bars represent 95% CIs for the SNP-based estimate, and vertical bars represent 95% CIs for the family-based estimate. Dashed and solid lines represent the observed (obtained by linear regression) and expected relationship between family-based and SNP-based heritability, respectively.

**Fig. 4.. Genetic correlations of same-sex sexual behavior with various preselected traits and disorders, separately for males and females.**
Males, green; females, blue. Yellow asterisks denote the genetic correlations that were experiment-wise significant (P < 8.9 × 10⁻⁴; references, definitions, and full results can be found in table S19). Wald test P values for the genetic correlations are reported above each dot. Horizontal bars represent 95% CIs.

**Fig. 5.. Complexity and heterogeneity of genetic influences.**
(A)Genetic correlations between the main phenotype (same-sex sexual behavior; heterosexuals versus nonheterosexuals) and proportion of same-sex to total sexual partners among nonheterosexuals, in the UK Biobank and 23andMe samples. (B) Scatterplot showing genetic correlations of the main phenotype (x axis) and the proportion of same-sex to total partners among nonheterosexuals (y axis) with various other traits (table S21). (C) Genetic correlations among different sexual preference items in the 23andMe sample.

See this image and copyright information in PMC

Comment in

How do genes affect same-sex behavior?
Mills MC. Mills MC. Science. 2019 Aug 30;365(6456):869-870. doi: 10.1126/science.aay2726. Science. 2019. PMID: 31467212 No abstract available.
No 'gay gene': Massive study homes in on genetic basis of human sexuality.
Lambert J. Lambert J. Nature. 2019 Sep;573(7772):14-15. doi: 10.1038/d41586-019-02585-6. Nature. 2019. PMID: 31481774 No abstract available.
Controversial 'gay gene' app provokes fears of a genetic Wild West.
Maxmen A. Maxmen A. Nature. 2019 Oct;574(7780):609-610. doi: 10.1038/d41586-019-03282-0. Nature. 2019. PMID: 31664219 No abstract available.
Genome studies reveal flaws in broad consent.
Holm S, Ploug T. Holm S, et al. Science. 2019 Dec 20;366(6472):1460-1461. doi: 10.1126/science.aaz3797. Science. 2019. PMID: 31857475 No abstract available.
Genome studies must account for history.
Richardson SS, Borsa A, Boulicault M, Galka J, Ghosh N, Gompers A, Noll NE, Perret M, Reiches MW, Sandoval JCB, Shattuck-Heidorn H, Vitti J, Weir B, Zhao H. Richardson SS, et al. Science. 2019 Dec 20;366(6472):1461. doi: 10.1126/science.aaz6594. Science. 2019. PMID: 31857476 No abstract available.
Comment on "Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior".
Hamer D, Mustanski B, Sell R, Sanders SA, Garcia JR. Hamer D, et al. Science. 2021 Mar 26;371(6536):eaba2941. doi: 10.1126/science.aba2941. Science. 2021. PMID: 33766855

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Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

Affiliations

Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

Authors

Affiliations

Abstract

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