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

被引：215

作者：

Ganna, Andrea ^{[1
,2
,3
,4
]}

Verweij, Karin J. H. ^{[5
]}

Nivard, Michel G. ^{[6
]}

Maier, Robert ^{[1
,2
,3
]}

Wedow, Robbee ^{[1
,3
,7
,8
,9
,10
,11
]}

Busch, Alexander S. ^{[12
,13
,14
]}

Abdellaoui, Abdel ^{[5
]}

Guo, Shengru ^{[15
]}

Sathirapongsasuti, J. Fah ^{[16
]}

Lichtenstein, Paul ^{[4
]}

Lundstrom, Sebastian ^{[17
]}

Langstrom, Niklas ^{[4
]}

Auton, Adam ^{[16
]}

Harris, Kathleen Mullan ^{[18
,19
]}

Beecham, Gary W. ^{[15
]}

Martin, Eden R. ^{[15
]}

Sanders, Alan R. ^{[20
,21
]}

Perry, John R. B. ^{[12
]}

Neale, Benjamin M. ^{[1
,2
,3
]}

Zietsch, Brendan P. ^{[22
]}

Agee, M.

Alipanahi, B.

Auton, A.

Bell, R. K.

Bryc, K.

Elson, S. L.

Fontanillas, P.

Furlotte, N. A.

Hicks, B.

Huber, K. E.

Jewett, E. M.

Jiang, Y.

Kleinman, A.

Lin, K. -H.

Litterman, N. K.

McCreight, J. C.

McIntyre, M. H.

McManus, K. F.

Mountain, J. L.

Noblin, E. S.

Northover, C. A. M.

Pitts, S. J.

Poznik, G. D.

Shastri, A. J.

Shelton, J. F.

Shringarpure, S.

Tian, C.

Tung, J. Y.

Vacic, V.

Wang, X.

机构：

[1] Massachusetts Gen Hosp, Ctr Genom Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[2] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[3] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[4] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[5] Univ Amsterdam, AMC, Amsterdam Univ Med Ctr UMC, Dept Psychiat, Meibergdreef 5, NL-1105 AZ Amsterdam, Netherlands

[6] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands

[7] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA

[8] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[9] Univ Colorado, Dept Sociol, Boulder, CO 80309 USA

[10] Univ Colorado, Inst Behav Sci, Hlth & Soc Program & Populat Program, Boulder, CO 80309 USA

[11] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[12] Univ Cambridge, Inst Metab Sci, Sch Clin Med, MRC,Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England

[13] Univ Copenhagen, Rigshosp, Dept Growth & Reprod, Copenhagen, Denmark

[14] Rigshosp, Int Ctr Res & Res Training Endocrine Disrupt Male, Copenhagen, Denmark

[15] Univ Miami, Dept Human Genet, Miami, FL 33136 USA

[16] 23andMe, Mountain View, CA 94041 USA

[17] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Ctr Eth Law & Mental Hlth, Gothenburg, Sweden

[18] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27516 USA

[19] Univ N Carolina, Dept Sociol, Chapel Hill, NC 27599 USA

[20] NorthShore Univ HealthSyst Res Inst, Dept Psychiat & Behav Sci, Evanston, IL 60201 USA

[21] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA

[22] Univ Queensland, Sch Psychol, Ctr Psychol & Evolut, Brisbane, Qld 4072, Australia

来源：

SCIENCE | 2019年 / 365卷 / 6456期

基金：

瑞典研究理事会; 美国国家卫生研究院; 美国国家科学基金会; 澳大利亚研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; ORIENTATION; LINKAGE; DISEASE; LOCI; SCHIZOPHRENIA; TRAIT; HOMOSEXUALITY;

D O I：

10.1126/science.aat7693

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：882 / +

页数：95

共 106 条

[1] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[2]

[Anonymous], 1998, GENETICS ANAL QUANTI

[3] The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease [J].

Astle, William J. ;

Elding, Heather ;

Jiang, Tao ;

Allen, Dave ;

Ruklisa, Dace ;

Mann, Alice L. ;

Mead, Daniel ;

Bouman, Heleen ;

Riveros-Mckay, Fernando ;

Kostadima, Myrto A. ;

Lambourne, John J. ;

Sivapalaratnam, Suthesh ;

Downes, Kate ;

Kundu, Kousik ;

Bomba, Lorenzo ;

Berentsen, Kim ;

Bradley, John R. ;

Daugherty, Louise C. ;

Delaneau, Olivier ;

Freson, Kathleen ;

Garner, Stephen F. ;

Grassi, Luigi ;

Guerrero, Jose ;

Haimel, Matthias ;

Janssen-Megens, Eva M. ;

Kaan, Anita ;

Kamat, Mihir ;

Kim, Bowon ;

Mandoli, Amit ;

Marchini, Jonathan ;

Martens, Joost H. A. ;

Meacham, Stuart ;

Megy, Karyn ;

O'Connell, Jared ;

Petersen, Romina ;

Sharifi, Nilofar ;

Sheard, Simon M. ;

Staley, James R. ;

Tuna, Salih ;

van der Ent, Martijn ;

Walter, Klaudia ;

Wang, Shuang-Yin ;

Wheeler, Eleanor ;

Wilder, Steven P. ;

Iotchkova, Valentina ;

Moore, Carmel ;

Sambrook, Jennifer ;

Stunnenberg, Hendrik G. ;

Di Angelantonio, Emanuele ;

Kaptoge, Stephen .

CELL, 2016, 167 (05) :1415-+

[4] Sexual Orientation, Controversy, and Science [J].

Bailey, J. Michael ;

Vasey, Paul L. ;

Diamond, Lisa M. ;

Breedlove, S. Marc ;

Vilain, Eric ;

Epprecht, Marc .

PSYCHOLOGICAL SCIENCE IN THE PUBLIC INTEREST, 2016, 17 (02) :45-101

[5] Genetic and environmental influences on sexual orientation and its correlates in an Australian twin sample [J].

Bailey, JM ;

Dunne, MP ;

Martin, NG .

JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY, 2000, 78 (03) :524-536

[6] Genome-wide analysis identifies 12 loci influencing human reproductive behavior [J].

Barban, Nicola ;

Jansen, Rick ;

de Vlaming, Ronald ;

Vaez, Ahmad ;

Mandemakers, Jornt J. ;

Tropf, Felix C. ;

Shen, Xia ;

Wilson, James F. ;

Chasman, Daniel I. ;

Nolte, Illa M. ;

Tragante, Vinicius ;

van der Laan, Sander W. ;

Perry, John R. B. ;

Kong, Augustine ;

Ahluwalia, Tarunveer S. ;

Albrecht, Eva ;

Yerges-Armstrong, Laura ;

Atzmon, Gil ;

Auro, Kirsi ;

Ayers, Kristin ;

Bakshi, Andrew ;

Ben-Avraham, Danny ;

Berger, Klaus ;

Bergman, Aviv ;

Bertram, Lars ;

Bielak, Lawrence F. ;

Bjornsdottir, Gyda ;

Bonder, Marc Jan ;

Broer, Linda ;

Bui, Minh ;

Barbieri, Caterina ;

Cavadino, Alana ;

Chavarro, Jorge E. ;

Turman, Constance ;

Concas, Maria Pina ;

Cordell, Heather J. ;

Davies, Gail ;

Eibich, Peter ;

Eriksson, Nicholas ;

Esko, Tonu ;

Eriksson, Joel ;

Falahi, Fahimeh ;

Felix, Janine F. ;

Fontana, Mark Alan ;

Franke, Lude ;

Gandin, Ilaria ;

Gaskins, Audrey J. ;

Gieger, Christian ;

Gunderson, Erica P. ;

Guo, Xiuqing .

NATURE GENETICS, 2016, 48 (12) :1462-1472

[7] Basic Helix-Loop-Helix Transcription Factor TCF21 Is a Downstream Target of the Male Sex Determining Gene SRY [J].

Bhandari, Ramji K. ;

Sadler-Riggleman, Ingrid ;

Clement, Tracy M. ;

Skinner, Michael K. .

PLOS ONE, 2011, 6 (05)

[8] A genome-wide association study of anorexia nervosa [J].

Boraska, V. ;

Franklin, C. S. ;

Floyd, J. A. B. ;

Thornton, L. M. ;

Huckins, L. M. ;

Southam, L. ;

Rayner, N. W. ;

Tachmazidou, I. ;

Klump, K. L. ;

Treasure, J. ;

Lewis, C. M. ;

Schmidt, U. ;

Tozzi, F. ;

Kiezebrink, K. ;

Hebebrand, J. ;

Gorwood, P. ;

Adan, R. A. H. ;

Kas, M. J. H. ;

Favaro, A. ;

Santonastaso, P. ;

Fernandez-Aranda, F. ;

Gratacos, M. ;

Rybakowski, F. ;

Dmitrzak-Weglarz, M. ;

Kaprio, J. ;

Keski-Rahkonen, A. ;

Raevuori, A. ;

Van Furth, E. F. ;

't Landt, M. C. T. Slof-Op ;

Hudson, J. I. ;

Reichborn-Kjennerud, T. ;

Knudsen, G. P. S. ;

Monteleone, P. ;

Kaplan, A. S. ;

Karwautz, A. ;

Hakonarson, H. ;

Berrettini, W. H. ;

Guo, Y. ;

Li, D. ;

Schork, N. J. ;

Komaki, G. ;

Ando, T. ;

Inoko, H. ;

Esko, T. ;

Fischer, K. ;

Maennik, K. ;

Metspalu, A. ;

Baker, J. H. ;

Cone, R. D. ;

Dackor, J. .

MOLECULAR PSYCHIATRY, 2014, 19 (10) :1085-1094

[9] An atlas of genetic correlations across human diseases and traits [J].

Bulik-Sullivan, Brendan ;

Finucane, Hilary K. ;

Anttila, Verneri ;

Gusev, Alexander ;

Day, Felix R. ;

Loh, Po-Ru ;

Duncan, Laramie ;

Perry, John R. B. ;

Patterson, Nick ;

Robinson, Elise B. ;

Daly, Mark J. ;

Price, Alkes L. ;

Neale, Benjamin M. .

NATURE GENETICS, 2015, 47 (11) :1236-+

[10] LD Score regression distinguishes confounding from polygenicity in genome-wide association studies [J].

Bulik-Sullivan, Brendan K. ;

Loh, Po-Ru ;

Finucane, Hilary K. ;

Ripke, Stephan ;

Yang, Jian ;

Patterson, Nick ;

Daly, Mark J. ;

Price, Alkes L. ;

Neale, Benjamin M. .

NATURE GENETICS, 2015, 47 (03) :291-+

← 1 2 3 4 5 6 7 8 9 10 →