Genome-wide analysis identifies 12 loci influencing human reproductive behavior

被引：179

作者：

Barban, Nicola ^{[1
,2
]}

Jansen, Rick ^{[3
]}

de Vlaming, Ronald ^{[4
,5
,6
]}

Vaez, Ahmad ^{[7
,8
]}

Mandemakers, Jornt J. ^{[9
]}

Tropf, Felix C. ^{[1
,2
]}

Shen, Xia ^{[10
,11
,12
]}

Wilson, James F. ^{[11
,12
]}

Chasman, Daniel I. ^{[13
,14
]}

Nolte, Illa M. ^{[7
]}

Tragante, Vinicius ^{[15
]}

van der Laan, Sander W. ^{[16
]}

Perry, John R. B. ^{[17
]}

Kong, Augustine ^{[18
,19
]}

Ahluwalia, Tarunveer S. ^{[20
,21
,22
]}

Albrecht, Eva ^{[23
]}

Yerges-Armstrong, Laura ^{[24
]}

Atzmon, Gil ^{[25
,26
,27
,28
]}

Auro, Kirsi ^{[29
,30
]}

Ayers, Kristin ^{[31
]}

Bakshi, Andrew ^{[32
]}

Ben-Avraham, Danny ^{[27
]}

Berger, Klaus ^{[33
]}

Bergman, Aviv ^{[34
,35
,36
]}

Bertram, Lars ^{[37
,38
,39
]}

Bielak, Lawrence F. ^{[40
]}

Bjornsdottir, Gyda ^{[19
]}

Bonder, Marc Jan ^{[41
]}

Broer, Linda ^{[42
]}

Bui, Minh ^{[43
]}

Barbieri, Caterina ^{[44
]}

Cavadino, Alana ^{[45
,46
]}

Chavarro, Jorge E. ^{[47
,48
,49
,50
]}

Turman, Constance ^{[50
]}

Concas, Maria Pina ^{[51
]}

Cordell, Heather J. ^{[31
]}

Davies, Gail ^{[52
,53
]}

Eibich, Peter ^{[54
]}

Eriksson, Nicholas ^{[55
]}

Esko, Tonu ^{[57
]}

Eriksson, Joel ^{[58
]}

Falahi, Fahimeh ^{[7
]}

Felix, Janine F. ^{[5
,59
,60
]}

Fontana, Mark Alan ^{[61
]}

Franke, Lude ^{[41
]}

Gandin, Ilaria ^{[62
]}

Gaskins, Audrey J. ^{[47
]}

Gieger, Christian ^{[63
,64
]}

Gunderson, Erica P. ^{[65
]}

Guo, Xiuqing ^{[66
]}

机构：

[1] Univ Oxford, Dept Sociol, Oxford, England

[2] Univ Oxford, Nuffield Coll, Oxford, England

[3] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[4] Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands

[5] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[6] Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands

[7] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[8] Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Esfahan, Iran

[9] Wageningen Univ Res, Sociol Consumpt & Households, Wageningen, Netherlands

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

[11] Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

[12] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland

[13] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[14] Harvard Med Sch, Boston, MA USA

[15] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands

[16] Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands

[17] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[18] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland

[19] Amgen Inc, deCODE Genet, Reykjavik, Iceland

[20] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[21] Steno Diabet Ctr, Gentofte, Denmark

[22] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark

[23] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany

[24] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[25] Albert Einstein Coll Med, Dept Med, Inst Aging Res, Bronx, NY 10467 USA

[26] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA

[27] Albert Einstein Coll Med, Inst Aging Res, Dept Genet, Bronx, NY 10467 USA

[28] Univ Haifa, Dept Nat Sci, Haifa, Israel

[29] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland

[30] Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland

[31] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England

[32] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[33] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany

[34] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10467 USA

[35] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA

[36] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA

[37] Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Inst Neurogenet, Lubeck, Germany

[38] Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany

[39] Imperial Coll, Fac Med, Sch Publ Hlth, London, England

[40] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA

[41] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Genom Coordinat Ctr, Groningen, Netherlands

[42] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[43] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

[44] San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy

[45] UCL Inst Child Hlth, Populat Policy & Practice, London, England

[46] Queen Mary Univ London, Wolfson Inst Preventat Med, Ctr Environm & Prevent Med, London, England

[47] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA

[48] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[49] Harvard Med Sch, Boston, MA USA

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

来源：

NATURE GENETICS | 2016年 / 48卷 / 12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; 欧洲研究理事会; 英国惠康基金;

关键词：

POLYCYSTIC-OVARY-SYNDROME; GENE POLYMORPHISMS; QUALITY-CONTROL; HUMAN-DISEASES; ASSOCIATION; FERTILITY; INSIGHTS; PROTEIN; MOUSE; TRANSLOCATION;

D O I：

10.1038/ng.3698

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

引用

页码：1462 / 1472

页数：11

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