Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

Lisette Stolk; John R.B. Perry; Daniel I. Chasman; Chunyan He; Massimo Mangino; Patrick Sulem; Maja Barbalic; Linda Broer; Enda M. Byrne; Florian Ernst; Tmu Esko; Nora Franceschini; Daniel F. Gudbjartsson; Jouke Jan Hottenga; Peter Kraft; Patrick F. McArdle; Eleonora Porcu; So Youn Shin; Albert V. Smith; Sophie Van Wingerden; Guangju Zhai; Wei V. Zhuang; Eva Albrecht; Behrooz Z. Alizadeh; Thor Aspelund; Stefania Bandinelli; Lovorka Barac Lauc; Jacques S. Beckmann; Mladen Boban; Eric Boerwinkle; Frank J. Broekmans; Andrea Burri; Harry Campbell; Stephen J. Chanock; Constance Chen; Marilyn C. Cornelis; Tanguy Corre; Andrea D. Coviello; Pio D'Adamo; Gail Davies; Ulf De Faire; Eco J.C. De Geus; Ian J. Deary; George V.Z. Dedoussis; Panagiotis Deloukas; Shah Ebrahim; Gudny Eiriksdottir; Valur Emilsson; Johan G. Eriksson; Bart C.J.M. Fauser; Liana Ferreli; Luigi Ferrucci; Krista Fischer; Aaron R. Folsom; Melissa E. Garcia; Paolo Gasparini; Christian Gieger; Nicole Glazer; Diederick E. Grobbee; Per Hall; Toomas Haller; Susan E. Hankinson; Merli Hass; Caroline Hayward; Andrew C. Heath; Albert Hofman; Erik Ingelsson; A. Cecile J.W. Janssens; Andrew D. Johnson; David Karasik; Sharon L.R. Kardia; Jules Keyzer; Douglas P. Kiel; Ivana Kolcic; Zoltn Kutalik; Jari Lahti; Sandra Lai; Triin Laisk; Joop S.E. Laven; Debbie A. Lawlor; Jianjun Liu; Lorna M. Lopez; Yvonne V. Louwers; Patrik K.E. Magnusson; Mara Marongiu; Nicholas G. Martin; Irena Martinovic Klaric; Corrado Masciullo; Barbara McKnight; Sarah E. Medland; David Melzer; Vincent Mooser; Pau Navarro; Anne B. Newman; Dale R. Nyholt; N. Charlotte Onland-Moret; Aarno Palotie; Guillaume Paré; Alex N. Parker; Nancy L. Pedersen; Petra H.M. Peeters; Giorgio Pistis; Andrew S. Plump; Ozren Polasek; Victor J.M. Pop; Bruce M. Psaty; Katri R Currency Signikkönen; Emil Rehnberg; Jerome I. Rotter; Igor Rudan; Cinzia Sala; Andres Salumets; Angelo Scuteri; Andrew Singleton; Jennifer A. Smith; Harold Snieder; Nicole Soranzo; Simon N. Stacey; John M. Starr; Maria G. Stathopoulou; Kathleen Stirrups; Ronald P. Stolk; Unnur Styrkarsdottir; Yan V. Sun; Albert Tenesa; Barbara Thorand; Daniela Toniolo; Laufey Tryggvadottir; Kim Tsui; Sheila Ulivi; Rob M. Van Dam; Yvonne T. Van Der Schouw; Carla H. Van Gils; Peter Van Nierop; Jacqueline M. Vink; Peter M. Visscher; Marlies Voorhuis; Gérard Waeber; Henri Wallaschofski; H. Erich Wichmann; Elisabeth Widen; Colette J.M. Wijnands-Van Gent; Gonneke Willemsen; James F. Wilson; Bruce H.R. Wolffenbuttel; Alan F. Wright; Laura M. Yerges-Armstrong; Tatijana Zemunik; Lina Zgaga; M. Carola Zillikens; Marek Zygmunt; Alice M. Arnold; Dorret I. Boomsma; Julie E. Buring; Laura Crisponi; Ellen W. Demerath; Vilmundur Gudnason; Tamara B. Harris; Frank B. Hu; David J. Hunter; Lenore J. Launer; Andres Metspalu; Grant W. Montgomery; Ben A. Oostra; Paul M. Ridker; Serena Sanna; David Schlessinger; Tim D. Spector; Kari Stefansson; Elizabeth A. Streeten; Unnur Thorsteinsdottir; Manuela Uda; André G. Uitterlinden; Cornelia M. Van Duijn; Henry Völzke; Anna Murray; Joanne M. Murabito; Jenny A. Visser; Kathryn L. Lunetta

doi:10.1038/ng.1051

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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

Lisette Stolk, John R.B. Perry, Daniel I. Chasman, Chunyan He, Massimo Mangino, Patrick Sulem, Maja Barbalic, Linda Broer, Enda M. Byrne, Florian Ernst, …

Nature genetics, Vol.44(3), pp.260-268

03/2012

DOI: https://doi.org/10.1038/ng.1051

PMCID: PMC3288642

PMID: 22267201

Abstract

Genetics

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P <5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

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Title: Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
Creators: Lisette Stolk (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Aging
John R.B. Perry (Author) - University of Exeter;University of Oxford
Daniel I. Chasman (Author) - Harvard University
Chunyan He (Author) - Indiana University Bloomington
Massimo Mangino (Author) - King's College London
Patrick Sulem (Author) - deCODE Genetics
Maja Barbalic (Author) - University of Texas Health Science Center at Houston
Linda Broer (Author) - Erasmus University Rotterdam
Enda M. Byrne (Author) - Queensland Institute of Medical Research
Florian Ernst (Author) - University of Greifswald
Tmu Esko (Author) - Estonian Biocentre;University of Tartu
Nora Franceschini (Author) - University of North Carolina at Chapel Hill
Daniel F. Gudbjartsson (Author) - deCODE Genetics
Jouke Jan Hottenga (Author) - Vrije Universiteit Amsterdam
Peter Kraft (Author) - Harvard University;Broad Institute
Patrick F. McArdle (Author) - University of Maryland, Baltimore
Eleonora Porcu (Author) - National Research Council of Italy
So Youn Shin (Author) - Wellcome Trust
Albert V. Smith (Author) - Icelandic Heart Association;University of Iceland
Sophie Van Wingerden (Author) - Erasmus University Rotterdam
Guangju Zhai (Author) - King's College London;Memorial University of Newfoundland
Wei V. Zhuang (Author) - Public Health
Eva Albrecht (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health
Behrooz Z. Alizadeh (Author) - University of Groningen
Thor Aspelund (Author) - Icelandic Heart Association;University of Iceland
Stefania Bandinelli (Author) - Azienda Sanitaria di Firenze
Lovorka Barac Lauc (Author) - Croatian Science Foundation
Jacques S. Beckmann (Author) - University of Lausanne
Mladen Boban (Author) - University of Split
Eric Boerwinkle (Author) - University of Texas Health Science Center at Houston
Frank J. Broekmans (Author) - Utrecht University
Andrea Burri (Author) - King's College London
Harry Campbell (Author) - University of Edinburgh
Stephen J. Chanock (Author) - National Institutes of Health
Constance Chen (Author) - Harvard University
Marilyn C. Cornelis (Author) - Harvard University
Tanguy Corre (Author) - IRCCS San Raffaele Scientific Institute
Andrea D. Coviello (Author) - Department of Medicine;National Heart, Lung, and Blood Institute's The Framingham Heart Study
Pio D'Adamo (Author) - IRCCS Ospedale Infantile Burlo Garofolo - Trieste;University of Trieste
Gail Davies (Author) - University of Edinburgh
Ulf De Faire (Author) - Karolinska Institutet
Eco J.C. De Geus (Author) - Vrije Universiteit Amsterdam;VU Medical Center
Ian J. Deary (Author) - University of Edinburgh
George V.Z. Dedoussis (Author) - Harokopio University
Panagiotis Deloukas (Author) - Wellcome Trust
Shah Ebrahim (Author) - London School of Hygiene and Tropical Medicine
Gudny Eiriksdottir (Author) - Icelandic Heart Association
Valur Emilsson (Author) - Icelandic Heart Association
Johan G. Eriksson (Author) - National Institute for Health and Welfare;Vaasa Hospital District
Bart C.J.M. Fauser (Author) - Utrecht University
Liana Ferreli (Author) - National Research Council of Italy
Luigi Ferrucci (Author) - National Institutes of Health
Krista Fischer (Author) - Estonian Biocentre
Aaron R. Folsom (Author) - University of Minnesota Twin Cities
Melissa E. Garcia (Author) - National Institutes of Health
Paolo Gasparini (Author) - IRCCS Ospedale Infantile Burlo Garofolo - Trieste;University of Trieste
Christian Gieger (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health
Nicole Glazer (Author) - Department of Medicine
Diederick E. Grobbee (Author) - Utrecht University
Per Hall (Author) - Karolinska Institutet
Toomas Haller (Author) - Estonian Biocentre
Susan E. Hankinson (Author) - Harvard University
Merli Hass (Author) - Estonian Biocentre
Caroline Hayward (Author) - University of Edinburgh
Andrew C. Heath (Author) - Washington University St. Louis
Albert Hofman (Author) - Netherlands Consortium of Healthy Aging;Erasmus University Rotterdam
Erik Ingelsson (Author) - Karolinska Institutet
A. Cecile J.W. Janssens (Author) - Erasmus University Rotterdam
Andrew D. Johnson (Author) - National Heart, Lung, and Blood Institute's The Framingham Heart Study
David Karasik (Author) - National Heart, Lung, and Blood Institute's The Framingham Heart Study;Harvard University
Sharon L.R. Kardia (Author) - University of Michigan, Ann Arbor
Jules Keyzer (Author) - Diagnostic GP Laboratory Eindhoven
Douglas P. Kiel (Author) - National Heart, Lung, and Blood Institute's The Framingham Heart Study;Harvard University
Ivana Kolcic (Author) - University of Split
Zoltn Kutalik (Author) - University of Lausanne;Swiss Institute of Bioinformatics
Jari Lahti (Author) - University of Helsinki
Sandra Lai (Author) - National Research Council of Italy
Triin Laisk (Author) - University of Tartu
Joop S.E. Laven (Author) - Erasmus University Rotterdam
Debbie A. Lawlor (Author) - University of Bristol
Jianjun Liu (Author) - Agency for Science, Technology and Research, Singapore
Lorna M. Lopez (Author) - University of Edinburgh
Yvonne V. Louwers (Author) - Erasmus University Rotterdam
Patrik K.E. Magnusson (Author) - Karolinska Institutet
Mara Marongiu (Author) - National Research Council of Italy
Nicholas G. Martin (Author) - Queensland Institute of Medical Research
Irena Martinovic Klaric (Author) - University of Zagreb
Corrado Masciullo (Author) - IRCCS San Raffaele Scientific Institute
Barbara McKnight (Author) - University of Washington
Sarah E. Medland (Author) - Queensland Institute of Medical Research
David Melzer (Author) - University of Exeter
Vincent Mooser (Author) - GlaxoSmithKline
Pau Navarro (Author) - University of Edinburgh
Anne B. Newman (Author) - University of Pittsburgh
Dale R. Nyholt (Author) - Queensland Institute of Medical Research
N. Charlotte Onland-Moret (Author) - Utrecht University
Aarno Palotie (Author) - Wellcome Trust;University of Helsinki
Guillaume Paré (Author) - Harvard University;McMaster University
Alex N. Parker (Author) - Amgen Incorporated;Foundation Medicine, Inc.
Nancy L. Pedersen (Author) - Karolinska Institutet
Petra H.M. Peeters (Author) - Utrecht University;Faculty of Medicine
Giorgio Pistis (Author) - IRCCS San Raffaele Scientific Institute
Andrew S. Plump (Author) - Merck
Ozren Polasek (Author) - University of Split
Victor J.M. Pop (Author) - Tilburg University
Bruce M. Psaty (Author) - University of Washington;Group Health Cooperative
Katri R Currency Signikkönen (Author) - University of Helsinki
Emil Rehnberg (Author) - Karolinska Institutet
Jerome I. Rotter (Author) - Cedars-Sinai Medical Center
Igor Rudan (Author) - University of Split;University of Edinburgh
Cinzia Sala (Author) - IRCCS San Raffaele Scientific Institute
Andres Salumets (Author) - Estonian Biocentre;University of Tartu;Competence Centre on Reproductive Medicine and Biology
Angelo Scuteri (Author) - National Institutes of Health, Bethesda
Andrew Singleton (Author) - National Institutes of Health
Jennifer A. Smith (Author) - University of Michigan, Ann Arbor
Harold Snieder (Author) - University of Groningen
Nicole Soranzo (Author) - King's College London;Wellcome Trust
Simon N. Stacey (Author) - deCODE Genetics
John M. Starr (Author) - University of Edinburgh
Maria G. Stathopoulou (Author) - Harokopio University;Université de Lorraine
Kathleen Stirrups (Author) - Wellcome Trust
Ronald P. Stolk (Author) - University of Groningen
Unnur Styrkarsdottir (Author) - deCODE Genetics
Yan V. Sun (Author) - Emory University
Albert Tenesa (Author) - University of Edinburgh
Barbara Thorand (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health
Daniela Toniolo (Author) - IRCCS San Raffaele Scientific Institute;National Research Council of Italy
Laufey Tryggvadottir (Author) - University of Iceland;Icelandic Cancer Registry
Kim Tsui (Author) - Amgen Incorporated
Sheila Ulivi (Author) - IRCCS Ospedale Infantile Burlo Garofolo - Trieste
Rob M. Van Dam (Author) - Harvard University;National University of Singapore
Yvonne T. Van Der Schouw (Author) - Utrecht University
Carla H. Van Gils (Author) - Utrecht University
Peter Van Nierop (Author) - Municipal Health Service Brabant-Zuidoost
Jacqueline M. Vink (Author) - Vrije Universiteit Amsterdam
Peter M. Visscher (Author) - University of Edinburgh;Queensland Institute of Medical Research
Marlies Voorhuis (Author) - Utrecht University
Gérard Waeber (Author) - University of Lausanne
Henri Wallaschofski (Author) - University of Greifswald
H. Erich Wichmann (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health;Ludwig Maximilian University of Munich
Elisabeth Widen (Author) - University of Helsinki
Colette J.M. Wijnands-Van Gent (Author) - POZOB Veldhoven
Gonneke Willemsen (Author) - Vrije Universiteit Amsterdam
James F. Wilson (Author) - University of Edinburgh
Bruce H.R. Wolffenbuttel (Author) - University of Groningen
Alan F. Wright (Author) - University of Edinburgh
Laura M. Yerges-Armstrong (Author) - University of Maryland, Baltimore
Tatijana Zemunik (Author) - University of Split
Lina Zgaga (Author) - University of Edinburgh;University of Zagreb
M. Carola Zillikens (Author) - Erasmus University Rotterdam
Marek Zygmunt (Author) - University of Greifswald
Alice M. Arnold (Author) - University of Washington
Dorret I. Boomsma (Author) - Vrije Universiteit Amsterdam;VU Medical Center
Julie E. Buring (Author) - Harvard University
Laura Crisponi (Author) - Harvard University;National Research Council of Italy
Ellen W. Demerath (Author) - University of Helsinki;University of Minnesota Twin Cities
Vilmundur Gudnason (Author) - Icelandic Heart Association;University of Iceland
Tamara B. Harris (Author) - National Institutes of Health
Frank B. Hu (Author) - Harvard University
David J. Hunter (Author) - Harvard University;Broad Institute
Lenore J. Launer (Author) - National Institutes of Health
Andres Metspalu (Author) - Estonian Biocentre;University of Tartu;Competence Centre on Reproductive Medicine and Biology
Grant W. Montgomery (Author) - Queensland Institute of Medical Research
Ben A. Oostra (Author) - Erasmus University Rotterdam
Paul M. Ridker (Author) - Harvard University
Serena Sanna (Author) - National Research Council of Italy;University of Helsinki
David Schlessinger (Author) - NIA
Tim D. Spector (Author) - King's College London
Kari Stefansson (Author) - deCODE Genetics;University of Iceland
Elizabeth A. Streeten (Author) - University of Maryland, Baltimore;Folkhalsan
Unnur Thorsteinsdottir (Author) - deCODE Genetics;University of Iceland
Manuela Uda (Author) - National Research Council of Italy
André G. Uitterlinden (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Aging
Cornelia M. Van Duijn (Author) - Netherlands Consortium of Healthy Aging
Henry Völzke (Author) - Estonian Biocentre
Anna Murray (Author) - University of Exeter;Ludwig Maximilian University of Munich
Joanne M. Murabito (Author) - Department of Medicine;National Heart, Lung, and Blood Institute's The Framingham Heart Study
Jenny A. Visser (Author) - Erasmus University Rotterdam;University of Greifswald
Kathryn L. Lunetta (Author) - Boston University;National Heart, Lung, and Blood Institute's The Framingham Heart Study
Publication Details: Nature genetics, Vol.44(3), pp.260-268
Series: 44
Number of pages: 9
Identifiers: 991005929803802656
Academic Unit: Master Public Health
Language: English
Resource Type: Journal article

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

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