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Genome-wide scan demonstrates significant linkage for male sexual orientation

Published online by Cambridge University Press:  17 November 2014

A. R. Sanders ,
E. R. Martin ,
G. W. Beecham ,
S. Guo ,
K. Dawood ,
G. Rieger ,
J. A. Badner ,
E. S. Gershon ,
R. S. Krishnappa  and
A. B. Kolundzija
...Show all authors
A. R. Sanders*
Affiliation:
Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, IL, USA Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
E. R. Martin
Affiliation:
Department of Human Genetics, University of Miami, Miami, FL, USA
G. W. Beecham
Affiliation:
Department of Human Genetics, University of Miami, Miami, FL, USA
S. Guo
Affiliation:
Department of Human Genetics, University of Miami, Miami, FL, USA
K. Dawood
Affiliation:
Department of Psychology, Pennsylvania State University, University Park, PA, USA
G. Rieger
Affiliation:
Department of Psychology, University of Essex, Colchester, England, UK
J. A. Badner
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
E. S. Gershon
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
R. S. Krishnappa
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Elmhurst, NY, USA
A. B. Kolundzija
Affiliation:
Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA
J. Duan
Affiliation:
Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, IL, USA Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
P. V. Gejman
Affiliation:
Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, IL, USA Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
J. M. Bailey
Affiliation:
Department of Psychology, Northwestern University, Evanston, IL, USA
*
*Address for correspondence: A. R. Sanders, M.D., Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, 1001 University Place, Evanston, IL 60201, USA. (Email: alan.sanders.md@gmail.com)
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Abstract

Background

Findings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28.

Method

We conducted a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908 analyzed individuals in 384 families), by far the largest study of its kind to date.

Results

We identified two regions of linkage: the pericentromeric region on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59), which overlaps with the second strongest region from a previous separate linkage scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum multipoint LOD = 2.76), which was also implicated in prior research.

Conclusions

Results, especially in the context of past studies, support the existence of genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development of male sexual orientation.

Keywords

Chromosome 8chromosome Xq28complex traitgenome-wide linkage scanhumanmale sexual orientation.
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 7 , May 2015 , pp. 1379 - 1388
Copyright
Copyright © Cambridge University Press 2014 

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References

Abecasis, GR, Cherny, SS, Cookson, WO, Cardon, LR (2002). Merlin – rapid analysis of dense genetic maps using sparse gene flow trees. Nature Genetics 30, 97–101.CrossRefGoogle ScholarPubMed
Alanko, K, Santtila, P, Harlaar, N, Witting, K, Varjonen, M, Jern, P, Johansson, A, von der Pahlen, B, Sandnabba, NK (2010). Common genetic effects of gender atypical behavior in childhood and sexual orientation in adulthood: a study of Finnish twins. Archives of Sexual Behavior 39, 81–92.Google Scholar
Bailey, JM, Bell, AP (1993). Familiality of female and male homosexuality. Behavior Genetics 23, 313–322.CrossRefGoogle ScholarPubMed
Bailey, JM, Benishay, DS (1993). Familial aggregation of female sexual orientation. American Journal of Psychiatry 150, 272–277.Google ScholarPubMed
Bailey, JM, Dunne, MP, Martin, NG (2000). Genetic and environmental influences on sexual orientation and its correlates in an Australian twin sample. Journal of Personality and Social Psychology 78, 524–536.CrossRefGoogle Scholar
Bailey, JM, Pillard, RC (1991). A genetic study of male sexual orientation. Archives of General Psychiatry 48, 1089–1096.CrossRefGoogle ScholarPubMed
Bailey, JM, Pillard, RC, Dawood, K, Miller, MB, Trivedi, S, Farrer, LA, Murphy, RL (1999). A family history study of male sexual orientation using three independent samples. Behavior Genetics 29, 79–86.CrossRefGoogle ScholarPubMed
Bailey, JM, Pillard, RC, Neale, MC, Agyei, Y (1993). Heritable factors influence sexual orientation in women. Archives of General Psychiatry 50, 217–223.Google Scholar
Baud, A, Hermsen, R, Guryev, V, Stridh, P, Graham, D, McBride, MW, Foroud, T, Calderari, S, Diez, M, Ockinger, J, Beyeen, AD, Gillett, A, Abdelmagid, N, Guerreiro-Cacais, AO, Jagodic, M, Tuncel, J, Norin, U, Beattie, E, Huynh, N, Miller, WH, Koller, DL, Alam, I, Falak, S, Osborne-Pellegrin, M, Martinez-Membrives, E, Canete, T, Blazquez, G, Vicens-Costa, E, Mont-Cardona, C, Diaz-Moran, S, Tobena, A, Hummel, O, Zelenika, D, Saar, K, Patone, G, Bauerfeind, A, Bihoreau, MT, Heinig, M, Lee, YA, Rintisch, C, Schulz, H, Wheeler, DA, Worley, KC, Muzny, DM, Gibbs, RA, Lathrop, M, Lansu, N, Toonen, P, Ruzius, FP, de Bruijn, E, Hauser, H, Adams, DJ, Keane, T, Atanur, SS, Aitman, TJ, Flicek, P, Malinauskas, T, Jones, EY, Ekman, D, Lopez-Aumatell, R, Dominiczak, AF, Johannesson, M, Holmdahl, R, Olsson, T, Gauguier, D, Hubner, N, Fernandez-Teruel, A, Cuppen, E, Mott, R, Flint, J (2013). Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nature Genetics 45, 767–775.Google ScholarPubMed
Bell, AP, Weinberg, MS (1978). Homosexualities: a Study of Diversity Among Men and Women. Simon and Schuster: New York.Google Scholar
Blanchard, R, Bogaert, AF (1996). Biodemographic comparisons of homosexual and heterosexual men in the Kinsey interview data. Archives of Sexual Behavior 25, 551–579.Google Scholar
Burri, A, Cherkas, L, Spector, T, Rahman, Q (2011). Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity. PLoS ONE 6, e21982.CrossRefGoogle ScholarPubMed
Camperio Ciani, A, Cermelli, P, Zanzotto, G (2008). Sexually antagonistic selection in human male homosexuality. PLoS ONE 3, e2282.Google Scholar
Camperio Ciani, AS, Fontanesi, L, Iemmola, F, Giannella, E, Ferron, C, Lombardi, L (2012). Factors associated with higher fecundity in female maternal relatives of homosexual men. Journal of Sexual Medicine 9, 2878–2887.Google Scholar
Cantor, JM, Blanchard, R, Paterson, AD, Bogaert, AF (2002). How many gay men owe their sexual orientation to fraternal birth order? Archives of Sexual Behavior 31, 63–71.CrossRefGoogle ScholarPubMed
Diamond, LM (2008 a). Female bisexuality from adolescence to adulthood: results from a 10-year longitudinal study. Developmental Psychology 44, 5–14.Google Scholar
Diamond, LM (2008 b). Sexual Fluidity: Understanding Women's Love and Desire. Harvard University Press: Cambridge, MA.Google Scholar
Ebstein, RP, Knafo, A, Mankuta, D, Chew, SH, Lai, PS (2012). The contributions of oxytocin and vasopressin pathway genes to human behavior. Hormones and Behavior 61, 359–379.Google Scholar
Gavrilets, S, Rice, WR (2006). Genetic models of homosexuality: generating testable predictions. Proceedings of the Royal Society of London, Series B: Biological Sciences 273, 3031–3038.Google ScholarPubMed
Hamer, DH, Hu, S, Magnuson, VL, Hu, N, Pattatucci, AM (1993). A linkage between DNA markers on the X chromosome and male sexual orientation. Science 261, 321–327.CrossRefGoogle ScholarPubMed
Havlicek, J, Roberts, SC (2009). MHC-correlated mate choice in humans: a review. Psychoneuroendocrinology 34, 497–512.Google Scholar
Hu, S, Pattatucci, AM, Patterson, C, Li, L, Fulker, DW, Cherny, SS, Kruglyak, L, Hamer, DH (1995). Linkage between sexual orientation and chromosome Xq28 in males but not in females. Nature Genetics 11, 248–256.CrossRefGoogle Scholar
Kendler, KS, Thornton, LM, Gilman, SE, Kessler, RC (2000). Sexual orientation in a U.S. national sample of twin and nontwin sibling pairs. American Journal of Psychiatry 157, 1843–1846.Google Scholar
Kinsey, AC, Pomeroy, WB, Martin, CE (1948). Sexual Behavior in the Human Male. W. B. Saunders Company: Philadelphia.Google Scholar
Kirk, KM, Bailey, JM, Dunne, MP, Martin, NG (2000). Measurement models for sexual orientation in a community twin sample. Behavior Genetics 30, 345–356.CrossRefGoogle Scholar
Kong, A, Cox, NJ (1997). Allele-sharing models: LOD scores and accurate linkage tests. American Journal of Human Genetics 61, 1179–1188.Google Scholar
Kong, A, Thorleifsson, G, Gudbjartsson, DF, Masson, G, Sigurdsson, A, Jonasdottir, A, Walters, GB, Gylfason, A, Kristinsson, KT, Gudjonsson, SA, Frigge, ML, Helgason, A, Thorsteinsdottir, U, Stefansson, K (2010). Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467, 1099–1103.Google Scholar
Lander, E, Kruglyak, L (1995). Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics 11, 241–247.Google Scholar
Langstrom, N, Rahman, Q, Carlstrom, E, Lichtenstein, P (2010). Genetic and environmental effects on same-sex sexual behavior: a population study of twins in Sweden. Archives of Sexual Behavior 39, 75–80.Google Scholar
Laumann, EO, Gagnon, JH, Michael, RT, Michaels, S (eds) (1994 a). Homosexuality. In The Social Organization of Sexuality: Sexual Practices in the United States, pp. 283–321. The University of Chicago Press: Chicago.Google Scholar
Laumann, EO, Gagnon, JH, Michael, RT, Michaels, S (1994 b). The Social Organization of Sexuality: Sexual Practices in the United States. University of Chicago Press: Chicago.Google Scholar
Laurie, CC, Doheny, KF, Mirel, DB, Pugh, EW, Bierut, LJ, Bhangale, T, Boehm, F, Caporaso, NE, Cornelis, MC, Edenberg, HJ, Gabriel, SB, Harris, EL, Hu, FB, Jacobs, KB, Kraft, P, Landi, MT, Lumley, T, Manolio, TA, McHugh, C, Painter, I, Paschall, J, Rice, JP, Rice, KM, Zheng, X, Weir, BS (2010). Quality control and quality assurance in genotypic data for genome-wide association studies. Genetic Epidemiology 34, 591–602.Google Scholar
MacIntyre, F, Estep, KW (1993). Sperm competition and the persistence of genes for male homosexuality. Biosystems 31, 223–233.Google Scholar
Mandiyan, VS, Coats, JK, Shah, NM (2005). Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nature Neuroscience 8, 1660–1662.Google Scholar
Milinski, M, Croy, I, Hummel, T, Boehm, T (2013). Major histocompatibility complex peptide ligands as olfactory cues in human body odour assessment. Proceedings of the Royal Society of London, Series B: Biological Sciences 280, 20122889.Google Scholar
Miller, EM (2000). Homosexuality, birth order, and evolution: toward an equilibrium reproductive economics of homosexuality. Archives of Sexual Behavior 29, 1–34.Google Scholar
Mueller, JL, Skaletsky, H, Brown, LG, Zaghlul, S, Rock, S, Graves, T, Auger, K, Warren, WC, Wilson, RK, Page, DC (2013). Independent specialization of the human and mouse X chromosomes for the male germ line. Nature Genetics 45, 1083–1087.Google Scholar
Murphy, TF (1997). Gay Science: the Ethics of Sexual Orientation Research. Columbia University Press: New York, NY.Google Scholar
Murphy, TF (2012). Ethics, Sexual Orientation, and Choices about Children. The MIT Press: Cambridge, MA.Google Scholar
Mustanski, BS, Chivers, ML, Bailey, JM (2002). A critical review of recent biological research on human sexual orientation. Annual Review of Sex Research 13, 89–140.Google Scholar
Mustanski, BS, Dupree, MG, Nievergelt, CM, Bocklandt, S, Schork, NJ, Hamer, DH (2005). A genomewide scan of male sexual orientation. Human Genetics 116, 272–278.Google Scholar
Nagata-Kuroiwa, R, Furutani, N, Hara, J, Hondo, M, Ishii, M, Abe, T, Mieda, M, Tsujino, N, Motoike, T, Yanagawa, Y, Kuwaki, T, Yamamoto, M, Yanagisawa, M, Sakurai, T (2011). Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory. PLoS ONE 6, e16972.Google Scholar
Pattatucci, AML, Hamer, DH (1995). Development and familiality of sexual orientation in females. Behavior Genetics 25, 407–420.Google Scholar
Pillard, RC, Bailey, JM (1998). Human sexual orientation has a heritable component. Human Biology 70, 347–365.Google Scholar
Pillard, RC, Weinrich, JD (1986). Evidence of familial nature of male homosexuality. Archives of General Psychiatry 43, 808–812.Google Scholar
Purcell, S, Neale, B, Todd-Brown, K, Thomas, L, Ferreira, MA, Bender, D, Maller, J, Sklar, P, de Bakker, PI, Daly, MJ, Sham, PC (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics 81, 559–575.CrossRefGoogle ScholarPubMed
Rahman, Q, Collins, A, Morrison, M, Orrells, JC, Cadinouche, K, Greenfield, S, Begum, S (2008). Maternal inheritance and familial fecundity factors in male homosexuality. Archives of Sexual Behavior 37, 962–969.Google Scholar
Ramagopalan, SV, Dyment, DA, Handunnetthi, L, Rice, GP, Ebers, GC (2010). A genome-wide scan of male sexual orientation. Journal of Human Genetics 55, 131–132.CrossRefGoogle ScholarPubMed
Rice, G, Anderson, C, Risch, N, Ebers, G (1999 a). Male homosexuality: absence of linkage to microsatellite markers at Xq28. Science 284, 665–667.Google Scholar
Rice, G, Risch, N, Ebers, G (1999 b). Genetics and male sexual orientation. Science 285, 803.Google Scholar
Risch, N (1990). Linkage strategies for genetically complex traits. II. The power of affected relative pairs. American Journal of Human Genetics 46, 229–241.Google ScholarPubMed
Sanders, AR, Cao, Q, Zhang, J, Badner, JA, Goldin, LR, Guroff, JJ, Gershon, ES, Gejman, PV (1998). Genetic Linkage Study of Male Homosexual Orientation. American Psychiatric Association: Toronto, Ontario, Canada.Google Scholar
Santtila, P, Sandnabba, NK, Harlaar, N, Varjonen, M, Alanko, K, von der Pahlen, B (2008). Potential for homosexual response is prevalent and genetic. Biological Psychology 77, 102–105.Google Scholar
Schwartz, G, Kim, RM, Kolundzija, AB, Rieger, G, Sanders, AR (2010). Biodemographic and physical correlates of sexual orientation in men. Archives of Sexual Behavior 39, 93–109.Google Scholar
Shi, J, Levinson, DF, Duan, J, Sanders, AR, Zheng, Y, Pe'er, I, Dudbridge, F, Holmans, PA, Whittemore, AS, Mowry, BJ, Olincy, A, Amin, F, Cloninger, CR, Silverman, JM, Buccola, NG, Byerley, WF, Black, DW, Crowe, RR, Oksenberg, JR, Mirel, DB, Kendler, KS, Freedman, R, Gejman, PV (2009). Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460, 753–757.Google Scholar
Spehr, M, Kelliher, KR, Li, XH, Boehm, T, Leinders-Zufall, T, Zufall, F (2006). Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands. Journal of Neuroscience: 26, 1961–1970.Google Scholar
Turner, S, Armstrong, LL, Bradford, Y, Carlson, CS, Crawford, DC, Crenshaw, AT, de Andrade, M, Doheny, KF, Haines, JL, Hayes, G, Jarvik, G, Jiang, L, Kullo, IJ, Li, R, Ling, H, Manolio, TA, Matsumoto, M, McCarty, CA, McDavid, AN, Mirel, DB, Paschall, JE, Pugh, EW, Rasmussen, LV, Wilke, RA, Zuvich, RL, Ritchie, MD (2011). Quality control procedures for genome-wide association studies. Current Protocols in Human Genetics, chapter 1, unit 19, 1–18.Google Scholar
Watanabe, N, Wada, M, Irukayama-Tomobe, Y, Ogata, Y, Tsujino, N, Suzuki, M, Furutani, N, Sakurai, T, Yamamoto, M (2012). A single nucleotide polymorphism of the neuropeptide B/W receptor-1 gene influences the evaluation of facial expressions. PLoS ONE 7, e35390.CrossRefGoogle ScholarPubMed
Wedekind, C, Seebeck, T, Bettens, F, Paepke, AJ (1995). MHC-dependent mate preferences in humans. Proceedings of the Royal Society of London, Series B: Biological Sciences 260, 245–249.Google Scholar
Wilson, EO (1975). Sociobiology: the New Synthesis. Harvard University Press: Cambridge.Google Scholar
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