. 2023 May;7(5):790-801.

doi: 10.1038/s41562-023-01528-6. Epub 2023 Mar 2.

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Iain Mathieson^#¹, Felix R Day^#², Nicola Barban^#³, Felix C Tropf^#^{4

5

6}, David M Brazel^#^{4

7}; eQTLGen Consortium; BIOS Consortium; Ahmad Vaez^{8

9}, Natalie van Zuydam¹⁰, Bárbara D Bitarello¹¹, Eugene J Gardner², Evelina T Akimova^{4

7}, Ajuna Azad¹², Sven Bergmann^{13

14

15}, Lawrence F Bielak¹⁶, Dorret I Boomsma^{17

18}, Kristina Bosak¹⁹, Marco Brumat²⁰, Julie E Buring^{21

22}, David Cesarini^{23

24

25}, Daniel I Chasman^{21

22}, Jorge E Chavarro^{26

27

28}, Massimiliano Cocca²⁹, Maria Pina Concas²⁹, George Davey Smith³⁰, Gail Davies³¹, Ian J Deary³¹, Tõnu Esko^{32

33}, Jessica D Faul³⁴; FinnGen Study; Oscar Franco^{35

36}, Andrea Ganna^{37

38}, Audrey J Gaskins³⁹, Andrea Gelemanovic⁴⁰, Eco J C de Geus¹⁷, Christian Gieger⁴¹, Giorgia Girotto^{20

29}, Bamini Gopinath⁴², Hans Jörgen Grabe⁴³, Erica P Gunderson⁴⁴, Caroline Hayward⁴⁵, Chunyan He^{46

47}, Diana van Heemst⁴⁸, W David Hill³¹, Eva R Hoffmann¹², Georg Homuth⁴⁹, Jouke Jan Hottenga¹⁷, Hongyang Huang²⁶, Elina Hyppӧnen^{50

51}, M Arfan Ikram³⁵, Rick Jansen⁵², Magnus Johannesson⁵³, Zoha Kamali^{8

9}, Sharon L R Kardia¹⁶, Maryam Kavousi³⁵, Annette Kifley⁴², Tuomo Kiiskinen^{37

54}, Peter Kraft^{26

55}, Brigitte Kühnel⁴¹, Claudia Langenberg², Gerald Liew⁴²; Lifelines Cohort Study; Penelope A Lind⁵⁶, Jian'an Luan², Reedik Mägi³², Patrik K E Magnusson⁵⁷, Anubha Mahajan^{58

59}, Nicholas G Martin⁶⁰, Hamdi Mbarek^{17

61}, Mark I McCarthy^{58

59}, George McMahon⁶², Sarah E Medland⁵⁶, Thomas Meitinger⁶³, Andres Metspalu^{32

64}, Evelin Mihailov³², Lili Milani³², Stacey A Missmer^{26

65

66}, Paul Mitchell⁴², Stine Møllegaard⁶⁷, Dennis O Mook-Kanamori^{68

69}, Anna Morgan²⁹, Peter J van der Most⁸, Renée de Mutsert⁶⁸, Matthias Nauck⁷⁰, Ilja M Nolte⁸, Raymond Noordam⁴⁸, Brenda W J H Penninx⁷¹, Annette Peters⁷², Patricia A Peyser¹⁶, Ozren Polašek^{40

73}, Chris Power⁷⁴, Ajka Pribisalic⁴⁰, Paul Redmond³¹, Janet W Rich-Edwards^{26

28

75}, Paul M Ridker^{21

22}, Cornelius A Rietveld^{76

77}, Susan M Ring³⁰, Lynda M Rose²¹, Rico Rueedi^{13

14}, Vallari Shukla¹², Jennifer A Smith^{16

34}, Stasa Stankovic², Kári Stefánsson⁷⁸, Doris Stöckl⁷², Konstantin Strauch^{79

80

81}, Morris A Swertz⁸², Alexander Teumer⁸³, Gudmar Thorleifsson⁷⁸, Unnur Thorsteinsdottir⁷⁸, A Roy Thurik^{76

77

84}, Nicholas J Timpson³⁰, Constance Turman²⁶, André G Uitterlinden^{76

85}, Melanie Waldenberger^{41

72}, Nicholas J Wareham², David R Weir³⁴, Gonneke Willemsen¹⁷, Jing Hau Zhao², Wei Zhao¹⁶, Yajie Zhao², Harold Snieder⁸, Marcel den Hoed¹⁰, Ken K Ong², Melinda C Mills^#^{86

87

88

89}, John R B Perry^#⁹⁰

Collaborators, Affiliations

Collaborators

Diana van Heemst, Peter J van der Most

Affiliations

¹ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mathi@pennmedicine.upenn.edu.
² MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
³ Alma Mater Studiorum University of Bologna, Bologna, Italy.
⁴ Nuffield College, University of Oxford, Oxford, UK.
⁵ École Nationale de la Statistique et de L'administration Économique (ENSAE), Paris, France.
⁶ Center for Research in Economics and Statistics (CREST), Paris, France.
⁷ Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK.
⁸ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁹ Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
¹⁰ Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden.
¹¹ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹³ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
¹⁴ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹⁵ Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
¹⁶ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
¹⁷ Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁸ Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, the Netherlands.
¹⁹ Psychiatric Hospital 'Sveti Ivan', Zagreb, Croatia.
²⁰ Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
²¹ Brigham and Women's Hospital, Boston, MA, USA.
²² Harvard Medical School, Boston, MA, USA.
²³ Department of Economics, New York University, New York, NY, USA.
²⁴ Research Institute for Industrial Economics, Stockholm, Sweden.
²⁵ National Bureau of Economic Research, Cambridge, MA, USA.
²⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁸ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁹ Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
³⁰ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
³¹ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
³² Estonian Genome Center, University of Tartu, Tartu, Estonia.
³³ Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
³⁴ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
³⁵ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
³⁶ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
³⁷ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
³⁸ Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁹ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁴⁰ University of Split School of Medicine, Split, Croatia.
⁴¹ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁴² Centre for Vision Research, Westmead Institute for Medical Research and Department of Ophthalmology, University of Sydney, Sydney, New South Wales, Australia.
⁴³ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁴⁴ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁴⁵ Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁴⁶ Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
⁴⁷ Department of Internal Medicine, Division of Medical Oncology, University of Kentucky College of Medicine, Lexington, KY, USA.
⁴⁸ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
⁴⁹ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
⁵⁰ Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, South Australia, Australia.
⁵¹ South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁵² Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
⁵³ Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
⁵⁴ National Institute for Health and Welfare, Helsinki, Finland.
⁵⁵ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵⁶ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁵⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁵⁸ Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
⁵⁹ Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁶⁰ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁶¹ Qatar Genome Programme, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.
⁶² School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁶³ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁶⁴ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
⁶⁵ Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁶⁶ Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
⁶⁷ Department of Sociology, University of Copenhagen, Copenhagen, Denmark.
⁶⁸ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
⁶⁹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
⁷⁰ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
⁷¹ Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands.
⁷² Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁷³ Algebra University College, Zagreb, Croatia.
⁷⁴ Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK.
⁷⁵ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷⁶ Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.
⁷⁷ Department of Applied Economics, Erasmus School of Economics, Rotterdam, the Netherlands.
⁷⁸ deCODE Genetics/Amgen Inc., Reykjavik, Iceland.
⁷⁹ Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany.
⁸⁰ Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁸¹ Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany.
⁸² Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁸³ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁸⁴ Montpellier Business School, Montpellier, France.
⁸⁵ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁸⁶ Nuffield College, University of Oxford, Oxford, UK. melinda.mills@nuffield.ox.ac.uk.
⁸⁷ Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK. melinda.mills@nuffield.ox.ac.uk.
⁸⁸ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. melinda.mills@nuffield.ox.ac.uk.
⁸⁹ Department of Economics, Econometrics and Finance, University of Groningen, Groningen, the Netherlands. melinda.mills@nuffield.ox.ac.uk.
⁹⁰ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK. john.perry@mrc-epid.cam.ac.uk.

^# Contributed equally.

PMID: 36864135
DOI: 10.1038/s41562-023-01528-6

Free article

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Iain Mathieson et al. Nat Hum Behav. 2023 May.

Free article

. 2023 May;7(5):790-801.

doi: 10.1038/s41562-023-01528-6. Epub 2023 Mar 2.

Authors

Collaborators

Diana van Heemst, Peter J van der Most

Affiliations

¹ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mathi@pennmedicine.upenn.edu.
² MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
³ Alma Mater Studiorum University of Bologna, Bologna, Italy.
⁴ Nuffield College, University of Oxford, Oxford, UK.
⁵ École Nationale de la Statistique et de L'administration Économique (ENSAE), Paris, France.
⁶ Center for Research in Economics and Statistics (CREST), Paris, France.
⁷ Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK.
⁸ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁹ Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
¹⁰ Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden.
¹¹ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹³ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
¹⁴ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹⁵ Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
¹⁶ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
¹⁷ Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁸ Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, the Netherlands.
¹⁹ Psychiatric Hospital 'Sveti Ivan', Zagreb, Croatia.
²⁰ Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
²¹ Brigham and Women's Hospital, Boston, MA, USA.
²² Harvard Medical School, Boston, MA, USA.
²³ Department of Economics, New York University, New York, NY, USA.
²⁴ Research Institute for Industrial Economics, Stockholm, Sweden.
²⁵ National Bureau of Economic Research, Cambridge, MA, USA.
²⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁸ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁹ Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
³⁰ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
³¹ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
³² Estonian Genome Center, University of Tartu, Tartu, Estonia.
³³ Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
³⁴ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
³⁵ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
³⁶ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
³⁷ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
³⁸ Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁹ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁴⁰ University of Split School of Medicine, Split, Croatia.
⁴¹ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁴² Centre for Vision Research, Westmead Institute for Medical Research and Department of Ophthalmology, University of Sydney, Sydney, New South Wales, Australia.
⁴³ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁴⁴ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁴⁵ Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁴⁶ Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
⁴⁷ Department of Internal Medicine, Division of Medical Oncology, University of Kentucky College of Medicine, Lexington, KY, USA.
⁴⁸ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
⁴⁹ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
⁵⁰ Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, South Australia, Australia.
⁵¹ South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁵² Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
⁵³ Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
⁵⁴ National Institute for Health and Welfare, Helsinki, Finland.
⁵⁵ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵⁶ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁵⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁵⁸ Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
⁵⁹ Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁶⁰ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁶¹ Qatar Genome Programme, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.
⁶² School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁶³ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁶⁴ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
⁶⁵ Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁶⁶ Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
⁶⁷ Department of Sociology, University of Copenhagen, Copenhagen, Denmark.
⁶⁸ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
⁶⁹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
⁷⁰ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
⁷¹ Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands.
⁷² Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁷³ Algebra University College, Zagreb, Croatia.
⁷⁴ Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK.
⁷⁵ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷⁶ Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.
⁷⁷ Department of Applied Economics, Erasmus School of Economics, Rotterdam, the Netherlands.
⁷⁸ deCODE Genetics/Amgen Inc., Reykjavik, Iceland.
⁷⁹ Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany.
⁸⁰ Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁸¹ Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany.
⁸² Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁸³ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁸⁴ Montpellier Business School, Montpellier, France.
⁸⁵ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁸⁶ Nuffield College, University of Oxford, Oxford, UK. melinda.mills@nuffield.ox.ac.uk.
⁸⁷ Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK. melinda.mills@nuffield.ox.ac.uk.
⁸⁸ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. melinda.mills@nuffield.ox.ac.uk.
⁸⁹ Department of Economics, Econometrics and Finance, University of Groningen, Groningen, the Netherlands. melinda.mills@nuffield.ox.ac.uk.
⁹⁰ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK. john.perry@mrc-epid.cam.ac.uk.

^# Contributed equally.

PMID: 36864135
DOI: 10.1038/s41562-023-01528-6

Abstract

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.

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References

1. Day, F. R. et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat. Commun. 6, 8464 (2015). - PubMed - DOI
1. Day, F. et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet. 14, e1007813 (2018). - PubMed - PMC - DOI
1. Censin, J. C., Bovijn, J., Holmes, M. V. & Lindgren, C. M. Commentary: Mendelian randomization and women’s health. Int. J. Epidemiol. 48, 830–833 (2019). - PubMed - PMC - DOI
1. O’Connor, L. J. et al. Extreme polygenicity of complex traits is explained by negative selection. Am. J. Hum. Genet. 105, 456–476 (2019). - PubMed - PMC - DOI
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Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Collaborators

Affiliations

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Authors

Collaborators

Affiliations

Abstract

References

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LinkOut - more resources

Full Text Sources

Research Materials

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