Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Nicola Barban¹, Rick Jansen², Ronald de Vlaming^{3

4

5}, Ahmad Vaez^{6

7}, Jornt J Mandemakers⁸, Felix C Tropf¹, Xia Shen^{9

10

11}, James F Wilson^{10

11}, Daniel I Chasman¹², Ilja M Nolte⁶, Vinicius Tragante¹³, Sander W van der Laan¹⁴, John R B Perry¹⁵, Augustine Kong^{16

17}; BIOS Consortium; Tarunveer S Ahluwalia^{18

19

20}, Eva Albrecht²¹, Laura Yerges-Armstrong²², Gil Atzmon^{23

24

25}, Kirsi Auro^{26

27}, Kristin Ayers²⁸, Andrew Bakshi²⁹, Danny Ben-Avraham²⁴, Klaus Berger³⁰, Aviv Bergman³¹, Lars Bertram^{32

33}, Lawrence F Bielak³⁴, Gyda Bjornsdottir¹⁷, Marc Jan Bonder³⁵, Linda Broer³⁶, Minh Bui³⁷, Caterina Barbieri³⁸, Alana Cavadino^{39

40}, Jorge E Chavarro^{41

42

43}, Constance Turman⁴³, Maria Pina Concas⁴⁴, Heather J Cordell²⁸, Gail Davies^{45

46}, Peter Eibich⁴⁷, Nicholas Eriksson⁴⁸, Tõnu Esko^{49

50}, Joel Eriksson⁵¹, Fahimeh Falahi⁶, Janine F Felix^{4

52

53}, Mark Alan Fontana⁵⁴, Lude Franke³⁵, Ilaria Gandin⁵⁵, Audrey J Gaskins⁴¹, Christian Gieger^{56

57}, Erica P Gunderson⁵⁸, Xiuqing Guo⁵⁹, Caroline Hayward¹⁰, Chunyan He⁶⁰, Edith Hofer^{61

62}, Hongyan Huang⁴³, Peter K Joshi¹¹, Stavroula Kanoni⁶³, Robert Karlsson⁹, Stefan Kiechl⁶⁴, Annette Kifley⁶⁵, Alexander Kluttig⁶⁶, Peter Kraft^{43

67}, Vasiliki Lagou^{68

69

70}, Cecile Lecoeur⁷¹, Jari Lahti^{72

73

74}, Ruifang Li-Gao⁷⁵, Penelope A Lind⁷⁶, Tian Liu⁷⁷, Enes Makalic³⁷, Crysovalanto Mamasoula²⁸, Lindsay Matteson⁷⁸, Hamdi Mbarek^{79

80}, Patrick F McArdle²², George McMahon⁸¹, S Fleur W Meddens^{5

82}, Evelin Mihailov⁴⁹, Mike Miller⁸³, Stacey A Missmer^{43

84}, Claire Monnereau^{4

52

53}, Peter J van der Most⁶, Ronny Myhre⁸⁵, Mike A Nalls⁸⁶, Teresa Nutile⁸⁷, Ioanna Panagiota Kalafati⁸⁸, Eleonora Porcu^{89

90}, Inga Prokopenko^{91

92

93}, Kumar B Rajan⁹⁴, Janet Rich-Edwards^{42

43

95}, Cornelius A Rietveld^{3

4

5}, Antonietta Robino⁹⁶, Lynda M Rose¹², Rico Rueedi^{97

98}, Kathleen A Ryan²², Yasaman Saba⁹⁹, Daniel Schmidt³⁷, Jennifer A Smith³⁴, Lisette Stolk³⁶, Elizabeth Streeten²², Anke Tönjes¹⁰⁰, Gudmar Thorleifsson¹⁷, Sheila Ulivi⁹⁶, Juho Wedenoja¹⁰¹, Juergen Wellmann³⁰, Peter Willeit^{64

102

103}, Jie Yao⁵⁹, Loic Yengo^{71

104}, Jing Hua Zhao¹⁵, Wei Zhao³⁴, Daria V Zhernakova³⁵, Najaf Amin⁴, Howard Andrews¹⁰⁵, Beverley Balkau⁷¹, Nir Barzilai²³, Sven Bergmann^{97

98}, Ginevra Biino¹⁰⁶, Hans Bisgaard²⁰, Klaus Bønnelykke²⁰, Dorret I Boomsma^{79

80}, Julie E Buring¹², Harry Campbell¹¹, Stefania Cappellani⁹⁶, Marina Ciullo^{87

107}, Simon R Cox^{45

46}, Francesco Cucca^{89

90}, Daniela Toniolo³⁸, George Davey-Smith¹⁰⁸, Ian J Deary^{45

46}, George Dedoussis⁸⁸, Panos Deloukas^{63

109}, Cornelia M van Duijn⁴, Eco J C de Geus^{79

80}, Johan G Eriksson^{74

110

111

112

113}, Denis A Evans⁹⁴, Jessica D Faul¹¹⁴, Cinzia Felicita Sala³⁸, Philippe Froguel⁷¹, Paolo Gasparini^{55

115}, Giorgia Girotto^{55

115}, Hans-Jörgen Grabe¹¹⁶, Karin Halina Greiser¹¹⁷, Patrick J F Groenen^{5

118}, Hugoline G de Haan⁷⁵, Johannes Haerting⁶⁶, Tamara B Harris¹¹⁹, Andrew C Heath¹²⁰, Kauko Heikkilä²⁷, Albert Hofman^{4

5

43}, Georg Homuth¹²¹, Elizabeth G Holliday^{122

123}, John Hopper³⁷, Elina Hyppönen^{39

124

125}, Bo Jacobsson^{85

126}, Vincent W V Jaddoe^{4

52

53}, Magnus Johannesson¹²⁷, Astanand Jugessur⁸⁵, Mika Kähönen¹²⁸, Eero Kajantie^{129

130

131}, Sharon L R Kardia³⁴, Bernard Keavney^{28

132}, Ivana Kolcic¹³³, Päivikki Koponen¹³⁴, Peter Kovacs¹³⁵, Florian Kronenberg¹³⁶, Zoltan Kutalik^{98

137}, Martina La Bianca⁹⁶, Genevieve Lachance¹³⁸, William G Iacono⁸³, Sandra Lai⁸⁹, Terho Lehtimäki¹³⁹, David C Liewald⁴⁵; LifeLines Cohort Study; Cecilia M Lindgren^{92

93

140

141}, Yongmei Liu¹⁴², Robert Luben¹⁴¹, Michael Lucht¹¹⁰, Riitta Luoto¹⁴³, Per Magnus⁸⁵, Patrik K E Magnusson⁹, Nicholas G Martin⁷⁶, Matt McGue^{83

144}, Ruth McQuillan¹¹, Sarah E Medland⁷⁶, Christa Meisinger^{57

145}, Dan Mellström⁵¹, Andres Metspalu^{49

146}, Michela Traglia³⁸, Lili Milani⁴⁹, Paul Mitchell⁶⁵, Grant W Montgomery^{120

147}, Dennis Mook-Kanamori^{75

148

149}, Renée de Mutsert⁷⁵, Ellen A Nohr¹⁵⁰, Claes Ohlsson⁵¹, Jørn Olsen¹⁵¹, Ken K Ong¹⁵, Lavinia Paternoster¹⁰⁸, Alison Pattie⁴⁶, Brenda W J H Penninx^{2

80}, Markus Perola^{26

27

49}, Patricia A Peyser³⁴, Mario Pirastu⁴⁴, Ozren Polasek¹³³, Chris Power³⁹, Jaakko Kaprio^{26

27

101}, Leslie J Raffel¹⁵², Katri Räikkönen⁷², Olli Raitakari¹⁵³, Paul M Ridker¹², Susan M Ring¹⁰⁸, Kathryn Roll⁵⁹, Igor Rudan¹¹, Daniela Ruggiero⁸⁷, Dan Rujescu¹⁵⁴, Veikko Salomaa²⁶, David Schlessinger¹⁵⁵, Helena Schmidt⁹⁹, Reinhold Schmidt⁶¹, Nicole Schupf¹⁵⁶, Johannes Smit^{2

80}, Rossella Sorice^{87

107}, Tim D Spector¹³⁸, John M Starr^{45

157}, Doris Stöckl¹⁵⁶, Konstantin Strauch^{21

158}, Michael Stumvoll^{100

135}, Morris A Swertz³⁵, Unnur Thorsteinsdottir^{17

159}, A Roy Thurik^{3

5

160}, Nicholas J Timpson¹⁰⁸, Joyce Y Tung⁴⁸, André G Uitterlinden^{3

5

36}, Simona Vaccargiu⁴⁴, Jorma Viikari¹⁶¹, Veronique Vitart¹⁰, Henry Völzke¹⁶², Peter Vollenweider¹⁶³, Dragana Vuckovic^{55

115}, Johannes Waage²⁰, Gert G Wagner¹⁶⁴, Jie Jin Wang⁶⁵, Nicholas J Wareham¹⁵, David R Weir¹¹⁴, Gonneke Willemsen^{79

80}, Johann Willeit⁶⁴, Alan F Wright¹⁰, Krina T Zondervan^{165

166}, Kari Stefansson^{17

159}, Robert F Krueger⁸³, James J Lee⁸³, Daniel J Benjamin^{54

167}, David Cesarini^{168

169}, Philipp D Koellinger^{3

5

82}, Marcel den Hoed¹⁷⁰, Harold Snieder⁶, Melinda C Mills¹

Affiliations

¹ Department of Sociology and Nuffield College, University of Oxford, Oxford, UK.
² Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
³ Department of Applied Economics, Erasmus School of Economics, Rotterdam, the Netherlands.
⁴ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵ Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.
⁶ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁷ Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
⁸ Sociology of Consumption and Households, Wageningen University Research, Wageningen, the Netherlands.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹⁰ MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹¹ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
¹² Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹³ Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁴ Laboratory of Experimental Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁵ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
¹⁶ School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
¹⁷ deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
¹⁸ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Steno Diabetes Center, Gentofte, Denmark.
²⁰ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
²¹ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
²² Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.
²³ Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.
²⁴ Department of Genetics, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.
²⁵ Department of Natural Science, University of Haifa, Haifa, Israel.
²⁶ Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
²⁷ Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
²⁸ Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
²⁹ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
³⁰ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
³¹ Departments of Systems and Computational Biology, of Pathology and of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
³² Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and of Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
³³ School of Public Health, Faculty of Medicine, Imperial College, London, UK.
³⁴ Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
³⁵ Department of Genetics, Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³⁶ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
³⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
³⁸ Division of Genetics and Cell Biology, San Raffaele Research Institute, Milan, Italy.
³⁹ Population, Policy and Practice, UCL Institute of Child Health, London, UK.
⁴⁰ Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK.
⁴¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁴² Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁴⁴ Institute of Genetic and Biomedical Research, National Research Council, UOS of Sassari, Sassari, Italy.
⁴⁵ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
⁴⁶ Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁴⁷ Health Economics Research Centre, University of Oxford, Oxford, UK.
⁴⁸ 23andMe, Inc., Mountain View, California, USA.
⁴⁹ Estonian Genome Center, University of Tartu, Tartu, Estonia.
⁵⁰ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁵¹ Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵² Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵³ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵⁴ Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.
⁵⁵ Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
⁵⁶ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵⁷ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵⁸ Cardiovascular and Metabolic Conditions Section, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
⁵⁹ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
⁶⁰ Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, Indiana, USA.
⁶¹ Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
⁶² Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
⁶³ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁶⁴ Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
⁶⁵ Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
⁶⁶ Institute of Medical Epidemiology, Biostatistics and Informatics, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
⁶⁷ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁶⁸ Department of Neurosciences, KU Leuven, Leuven, Belgium.
⁶⁹ Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
⁷⁰ Translational Immunology Laboratory, VIB, Leuven, Belgium.
⁷¹ University of Lille, CNRS, Institut Pasteur of Lille, Lille, France.
⁷² Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland.
⁷³ Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
⁷⁴ Folkhälsan Research Centre, Helsinki, Finland.
⁷⁵ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
⁷⁶ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Herston Brisbane, Queensland, Australia.
⁷⁷ Center for Lifespan Psychology, Max Planck Institute for Human Development and Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁷⁸ Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.
⁷⁹ Department of Biological Psychology, VU University, Amsterdam, the Netherlands.
⁸⁰ EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.
⁸¹ School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁸² Complex Trait Genetics, VU University, Amsterdam, the Netherlands.
⁸³ Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.
⁸⁴ Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁸⁵ Department of Genetics and Bioinformatics, Area of Health Data and Digitalization, Institute of Public Health, Oslo, Norway.
⁸⁶ Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
⁸⁷ Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples, Italy.
⁸⁸ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
⁸⁹ Istituto di Ricerca Genetica e Biomedica, CMR, Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
⁹⁰ Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
⁹¹ Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
⁹² Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹³ Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁹⁴ Rush University Medical Center, Chicago, Illinois, USA.
⁹⁵ Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁹⁶ Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
⁹⁷ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
⁹⁸ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁹⁹ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.
¹⁰⁰ Department of Medicine, University of Leipzig, Leipzig, Germany.
¹⁰¹ Department of Public Health, University of Helsinki, Helsinki, Finland.
¹⁰² King's British Heart Foundation Centre, King's College London, London, UK.
¹⁰³ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁰⁴ Centre for Neurogenetics and Statistical Genomics, University of Queensland, Brisbane, Queensland, Australia.
¹⁰⁵ Data Coordinating Center, New York State Psychiatric Institute, New York, New York, USA.
¹⁰⁶ Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.
¹⁰⁷ IRCCS Neuromed, Pozzilli, Isernia, Italy.
¹⁰⁸ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
¹⁰⁹ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
¹¹⁰ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
¹¹¹ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
¹¹² Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
¹¹³ Vasa Central Hospital, Vasa, Finland.
¹¹⁴ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
¹¹⁵ Division of Experimental Genetics, Sidra, Doha, Qatar.
¹¹⁶ Department of Psychiatry, University Medicine Greifswald, Greifswald, Germany.
¹¹⁷ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
¹¹⁸ Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
¹¹⁹ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.
¹²⁰ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹²¹ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
¹²² School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
¹²³ Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹²⁴ Centre for Population Health Research, Sansom Institute of Health Research and School of Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
¹²⁵ South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
¹²⁶ Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
¹²⁷ Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
¹²⁸ Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
¹²⁹ Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
¹³⁰ Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
¹³¹ Department of Obstetrics and Gynecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹³² Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
¹³³ Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
¹³⁴ Health Monitoring Unit, National Institute for Health and Welfare, Helsinki, Finland.
¹³⁵ IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
¹³⁶ Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
¹³⁷ Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
¹³⁸ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹³⁹ Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
¹⁴⁰ NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁴¹ Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.
¹⁴² Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
¹⁴³ UKK Institute for Health Promotion,Tampere, Finland.
¹⁴⁴ Danish Aging Research Center and Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
¹⁴⁵ MONICA/KORA Myocardial Infarction Registry, Central Hospital of Augsburg, Augsburg, Germany.
¹⁴⁶ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
¹⁴⁷ Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
¹⁴⁸ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
¹⁴⁹ Department of BESC, Epidemiology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
¹⁵⁰ Research Unit for Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
¹⁵¹ Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
¹⁵² Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
¹⁵³ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
¹⁵⁴ Department of Psychiatry, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
¹⁵⁵ Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.
¹⁵⁶ Departments of Epidemiology and Psychiatry, Columbia University Medical Center, New York, New York, USA.
¹⁵⁷ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
¹⁵⁸ Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians Universität, Munich, Germany.
¹⁵⁹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹⁶⁰ Montpellier Business School, Montpellier, France.
¹⁶¹ Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
¹⁶² Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
¹⁶³ Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
¹⁶⁴ German Socio-Economic Panel Study (SOEP), Max Planck Institute for Human Development and Berlin University of Technology (TUB), Berlin, Germany.
¹⁶⁵ Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
¹⁶⁶ Endometriosis CaRe Centre, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
¹⁶⁷ National Bureau of Economic Research, Cambridge, Massachusetts, USA.
¹⁶⁸ Department of Economics, New York University, New York, New York, USA.
¹⁶⁹ Research Institute for Industrial Economics, Stockholm, Sweden.
¹⁷⁰ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

PMID: 27798627
PMCID: PMC5695684
DOI: 10.1038/ng.3698

Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Nicola Barban et al. Nat Genet. 2016 Dec.

. 2016 Dec;48(12):1462-1472.

doi: 10.1038/ng.3698. Epub 2016 Oct 31.

Authors

Affiliations

¹ Department of Sociology and Nuffield College, University of Oxford, Oxford, UK.
² Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
³ Department of Applied Economics, Erasmus School of Economics, Rotterdam, the Netherlands.
⁴ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵ Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.
⁶ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁷ Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
⁸ Sociology of Consumption and Households, Wageningen University Research, Wageningen, the Netherlands.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹⁰ MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹¹ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
¹² Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹³ Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁴ Laboratory of Experimental Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
¹⁵ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
¹⁶ School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
¹⁷ deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
¹⁸ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Steno Diabetes Center, Gentofte, Denmark.
²⁰ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
²¹ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
²² Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.
²³ Department of Medicine, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.
²⁴ Department of Genetics, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.
²⁵ Department of Natural Science, University of Haifa, Haifa, Israel.
²⁶ Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
²⁷ Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
²⁸ Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
²⁹ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
³⁰ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
³¹ Departments of Systems and Computational Biology, of Pathology and of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
³² Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and of Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
³³ School of Public Health, Faculty of Medicine, Imperial College, London, UK.
³⁴ Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
³⁵ Department of Genetics, Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³⁶ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
³⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
³⁸ Division of Genetics and Cell Biology, San Raffaele Research Institute, Milan, Italy.
³⁹ Population, Policy and Practice, UCL Institute of Child Health, London, UK.
⁴⁰ Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK.
⁴¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁴² Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁴⁴ Institute of Genetic and Biomedical Research, National Research Council, UOS of Sassari, Sassari, Italy.
⁴⁵ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
⁴⁶ Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁴⁷ Health Economics Research Centre, University of Oxford, Oxford, UK.
⁴⁸ 23andMe, Inc., Mountain View, California, USA.
⁴⁹ Estonian Genome Center, University of Tartu, Tartu, Estonia.
⁵⁰ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁵¹ Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵² Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵³ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵⁴ Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.
⁵⁵ Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
⁵⁶ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵⁷ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵⁸ Cardiovascular and Metabolic Conditions Section, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
⁵⁹ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
⁶⁰ Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, Indiana, USA.
⁶¹ Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
⁶² Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
⁶³ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁶⁴ Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
⁶⁵ Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
⁶⁶ Institute of Medical Epidemiology, Biostatistics and Informatics, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
⁶⁷ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁶⁸ Department of Neurosciences, KU Leuven, Leuven, Belgium.
⁶⁹ Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
⁷⁰ Translational Immunology Laboratory, VIB, Leuven, Belgium.
⁷¹ University of Lille, CNRS, Institut Pasteur of Lille, Lille, France.
⁷² Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland.
⁷³ Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
⁷⁴ Folkhälsan Research Centre, Helsinki, Finland.
⁷⁵ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
⁷⁶ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Herston Brisbane, Queensland, Australia.
⁷⁷ Center for Lifespan Psychology, Max Planck Institute for Human Development and Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁷⁸ Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.
⁷⁹ Department of Biological Psychology, VU University, Amsterdam, the Netherlands.
⁸⁰ EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.
⁸¹ School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁸² Complex Trait Genetics, VU University, Amsterdam, the Netherlands.
⁸³ Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.
⁸⁴ Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁸⁵ Department of Genetics and Bioinformatics, Area of Health Data and Digitalization, Institute of Public Health, Oslo, Norway.
⁸⁶ Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
⁸⁷ Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples, Italy.
⁸⁸ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
⁸⁹ Istituto di Ricerca Genetica e Biomedica, CMR, Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
⁹⁰ Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
⁹¹ Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
⁹² Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹³ Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁹⁴ Rush University Medical Center, Chicago, Illinois, USA.
⁹⁵ Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁹⁶ Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
⁹⁷ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
⁹⁸ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁹⁹ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.
¹⁰⁰ Department of Medicine, University of Leipzig, Leipzig, Germany.
¹⁰¹ Department of Public Health, University of Helsinki, Helsinki, Finland.
¹⁰² King's British Heart Foundation Centre, King's College London, London, UK.
¹⁰³ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁰⁴ Centre for Neurogenetics and Statistical Genomics, University of Queensland, Brisbane, Queensland, Australia.
¹⁰⁵ Data Coordinating Center, New York State Psychiatric Institute, New York, New York, USA.
¹⁰⁶ Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.
¹⁰⁷ IRCCS Neuromed, Pozzilli, Isernia, Italy.
¹⁰⁸ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
¹⁰⁹ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
¹¹⁰ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
¹¹¹ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
¹¹² Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
¹¹³ Vasa Central Hospital, Vasa, Finland.
¹¹⁴ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
¹¹⁵ Division of Experimental Genetics, Sidra, Doha, Qatar.
¹¹⁶ Department of Psychiatry, University Medicine Greifswald, Greifswald, Germany.
¹¹⁷ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
¹¹⁸ Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
¹¹⁹ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.
¹²⁰ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹²¹ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
¹²² School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
¹²³ Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹²⁴ Centre for Population Health Research, Sansom Institute of Health Research and School of Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
¹²⁵ South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
¹²⁶ Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
¹²⁷ Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
¹²⁸ Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
¹²⁹ Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
¹³⁰ Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
¹³¹ Department of Obstetrics and Gynecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹³² Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
¹³³ Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
¹³⁴ Health Monitoring Unit, National Institute for Health and Welfare, Helsinki, Finland.
¹³⁵ IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
¹³⁶ Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
¹³⁷ Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
¹³⁸ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹³⁹ Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
¹⁴⁰ NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁴¹ Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.
¹⁴² Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
¹⁴³ UKK Institute for Health Promotion,Tampere, Finland.
¹⁴⁴ Danish Aging Research Center and Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
¹⁴⁵ MONICA/KORA Myocardial Infarction Registry, Central Hospital of Augsburg, Augsburg, Germany.
¹⁴⁶ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
¹⁴⁷ Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
¹⁴⁸ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
¹⁴⁹ Department of BESC, Epidemiology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
¹⁵⁰ Research Unit for Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
¹⁵¹ Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
¹⁵² Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
¹⁵³ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
¹⁵⁴ Department of Psychiatry, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
¹⁵⁵ Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.
¹⁵⁶ Departments of Epidemiology and Psychiatry, Columbia University Medical Center, New York, New York, USA.
¹⁵⁷ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
¹⁵⁸ Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians Universität, Munich, Germany.
¹⁵⁹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹⁶⁰ Montpellier Business School, Montpellier, France.
¹⁶¹ Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
¹⁶² Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
¹⁶³ Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
¹⁶⁴ German Socio-Economic Panel Study (SOEP), Max Planck Institute for Human Development and Berlin University of Technology (TUB), Berlin, Germany.
¹⁶⁵ Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
¹⁶⁶ Endometriosis CaRe Centre, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
¹⁶⁷ National Bureau of Economic Research, Cambridge, Massachusetts, USA.
¹⁶⁸ Department of Economics, New York University, New York, New York, USA.
¹⁶⁹ Research Institute for Industrial Economics, Stockholm, Sweden.
¹⁷⁰ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

PMID: 27798627
PMCID: PMC5695684
DOI: 10.1038/ng.3698

Abstract

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.

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Conflict of interest statement

COMPETING FINANCIAL INTERESTS

The authors declare no competing financial interests.

Figures

**Figure 1. Manhattan plots of SNPs for AFB (age at first birth) and NEB (number of children ever born) in single genomic control meta-analysis**
SNPs are plotted on the x-axis according to their position on each chromosome against association with AFB (panel a) and NEB (panel b). The solid blue line indicates the threshold for genome-wide significance (P<5x10⁻⁰⁸) and the red line, the threshold for suggestive hits (P<5x10⁻⁰⁶). Blue points indicate SNPs in a ±100 KB region around genome-wide significant hits. Gene labels are annotated as the nearby genes to the significant SNPs.

**Figure 2. Quantile-quantile plots of SNPs for AFB (panel a) and NEB (panel b) in single genomic control, meta-analysis**
The grey shaded areas in the Q-Q plots represent the 95% confidence bands around the P-values under the null hypothesis.

**Figure 3. Genetic overlap between AFB and NEB and other related traits**
Results from Linkage-Disequilibrium (LD) Score regressions: estimates of genetic correlation with developmental, reproductive, behavioral, neuropsychiatric and anthropometric phenotypes for which GWAS summary statistics were available in the public domain. The length of the bars indicates the estimates of genetic correlation. Grey error bars indicate 95% confidence intervals. The mark “*” indicates that the estimate of genetic correlation is statistically significant after controlling for multiple testing (P<0.05/27=1.85x10⁻³).

See this image and copyright information in PMC

References

1. Elks C, et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat Genet. 2010;42:1077–1085. - PMC - PubMed
1. Perry JRB, et al. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature. 2014;514:92–97. - PMC - PubMed
1. Rahmioglu N, et al. Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets. Hum Reprod Update. 2014;20:702–716. - PMC - PubMed
1. Day FR, et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun. 2015;6:8464. - PMC - PubMed
1. Mehta D, et al. Evidence for genetic overlap between schizophrenia and age at first birth in women. JAMA Psychiatry. 2016 - PMC - PubMed

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Genome-wide analysis identifies 12 loci influencing human reproductive behavior

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Genome-wide analysis identifies 12 loci influencing human reproductive behavior

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Abstract

Conflict of interest statement

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