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Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.
Mathieson, Iain; Day, Felix R; Barban, Nicola; Tropf, Felix C; Brazel, David M; Vaez, Ahmad; van Zuydam, Natalie; Bitarello, Bárbara D; Gardner, Eugene J; Akimova, Evelina T; Azad, Ajuna; Bergmann, Sven; Bielak, Lawrence F; Boomsma, Dorret I; Bosak, Kristina; Brumat, Marco; Buring, Julie E; Cesarini, David; Chasman, Daniel I; Chavarro, Jorge E; Cocca, Massimiliano; Concas, Maria Pina; Davey Smith, George; Davies, Gail; Deary, Ian J; Esko, Tõnu; Faul, Jessica D; Franco, Oscar; Ganna, Andrea; Gaskins, Audrey J; Gelemanovic, Andrea; de Geus, Eco J C; Gieger, Christian; Girotto, Giorgia; Gopinath, Bamini; Grabe, Hans Jörgen; Gunderson, Erica P; Hayward, Caroline; He, Chunyan; van Heemst, Diana; Hill, W David; Hoffmann, Eva R; Homuth, Georg; Hottenga, Jouke Jan; Huang, Hongyang; HyppÓ§nen, Elina; Ikram, M Arfan; Jansen, Rick; Johannesson, Magnus; Kamali, Zoha.
Afiliação
  • Mathieson I; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mathi@pennmedicine.upenn.edu.
  • Day FR; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Barban N; Alma Mater Studiorum University of Bologna, Bologna, Italy.
  • Tropf FC; Nuffield College, University of Oxford, Oxford, UK.
  • Brazel DM; École Nationale de la Statistique et de L'administration Économique (ENSAE), Paris, France.
  • Vaez A; Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK.
  • Gardner EJ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Akimova ET; Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Azad A; Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden.
  • Bergmann S; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Bielak LF; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Boomsma DI; Nuffield College, University of Oxford, Oxford, UK.
  • Bosak K; Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK.
  • Brumat M; DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Buring JE; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Cesarini D; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Chasman DI; Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
  • Chavarro JE; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
  • Cocca M; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Concas MP; Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, the Netherlands.
  • Davey Smith G; Psychiatric Hospital 'Sveti Ivan', Zagreb, Croatia.
  • Davies G; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
  • Deary IJ; Brigham and Women's Hospital, Boston, MA, USA.
  • Esko T; Harvard Medical School, Boston, MA, USA.
  • Faul JD; Department of Economics, New York University, New York, NY, USA.
  • Franco O; National Bureau of Economic Research, Cambridge, MA, USA.
  • Ganna A; Brigham and Women's Hospital, Boston, MA, USA.
  • Gaskins AJ; Harvard Medical School, Boston, MA, USA.
  • Gelemanovic A; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • de Geus EJC; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Gieger C; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Girotto G; Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
  • Gopinath B; Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
  • Grabe HJ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Gunderson EP; Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Hayward C; Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • He C; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • van Heemst D; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Hill WD; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
  • Homuth G; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Hottenga JJ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Huang H; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • HyppÓ§nen E; Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Ikram MA; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
  • Jansen R; University of Split School of Medicine, Split, Croatia.
  • Johannesson M; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Kamali Z; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Nat Hum Behav ; 7(5): 790-801, 2023 05.
Article em En | MEDLINE | ID: mdl-36864135
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reprodução / Fertilidade Tipo de estudo: Prognostic_studies Limite: Child / Female / Humans Idioma: En Revista: Nat Hum Behav Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reprodução / Fertilidade Tipo de estudo: Prognostic_studies Limite: Child / Female / Humans Idioma: En Revista: Nat Hum Behav Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos