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; Tonu 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; Zoltan 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 Pare; 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 Raikkonen; 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; Gerard 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; Andre G. Uitterlinden; Cornelia M. van Duijn; Henry Voelzke; Anna Murray; Joanne M. Murabito; Jenny A. Visser; Kathryn L. Lunetta; LifeLines Cohort Study

doi:10.1038/ng.1051

Back

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

Journal article

Peer reviewed

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-U55

01/03/2012

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

PMID: 22267201

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 10(-8)). 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-kappa B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Metrics

1 Record Views

See more details

Details

Title: Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
Creators - without role: Lisette Stolk - Erasmus MC
John R. B. Perry - University of Exeter
Daniel I. Chasman - Brigham and Women's Hospital
Chunyan He - Indiana University
Massimo Mangino - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Patrick Sulem - deCODE Genet, Reykjavik, Iceland
Maja Barbalic - Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX USA
Linda Broer - Erasmus MC
Enda M. Byrne
Florian Ernst - University of Greifswald
Tonu Esko - University of Tartu
Nora Franceschini - Supreme Council Of Health
Daniel F. Gudbjartsson - deCODE Genet, Reykjavik, Iceland
Jouke-Jan Hottenga - University of Amsterdam
Peter Kraft - Harvard University
Patrick F. McArdle - Supreme Council Of Health
Eleonora Porcu - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
So-Youn Shin - Wellcome Sanger Institute
Albert V. Smith - Iceland Heart Assoc, Kopavogur, Iceland
Sophie van Wingerden - Erasmus MC
Guangju Zhai - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Wei V. Zhuang - Boston University
Eva Albrecht - Helmholtz Zentrum München
Behrooz Z. Alizadeh - University of Groningen
Thor Aspelund - Iceland Heart Assoc, Kopavogur, Iceland
Stefania Bandinelli - Florence
Lovorka Barac Lauc - Croatian Sci Fdn, Zagreb, Croatia
Jacques S. Beckmann - University of Lausanne
Mladen Boban - University of Split
Eric Boerwinkle - Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX USA
Frank J. Broekmans - College Station Medical Center
Andrea Burri - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Harry Campbell - University of Edinburgh
Stephen J. Chanock - NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA
Constance Chen - Harvard University
Marilyn C. Cornelis - Harvard University
Tanguy Corre - Mylan
Andrea D. Coviello - Boston University
Pio d'Adamo - Ist Ricovero & Cura Carattere Sci Materno Infanti, Inst Maternal & Child Hlth, Trieste, Italy
Gail Davies - University of Edinburgh
Ulf de Faire - Karolinska Institutet
Eco J. C. de Geus - University of Amsterdam
Ian J. Deary - University of Edinburgh
George V. Z. Dedoussis - Harokopio University of Athens
Panagiotis Deloukas - Wellcome Sanger Institute
Shah Ebrahim - Supreme Council Of Health
Gudny Eiriksdottir - Iceland Heart Assoc, Kopavogur, Iceland
Valur Emilsson - Iceland Heart Assoc, Kopavogur, Iceland
Johan G. Eriksson - Natl Inst Hlth & Welf, Helsinki, Finland
Bart C. J. M. Fauser - College Station Medical Center
Liana Ferreli - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
Luigi Ferrucci - NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA
Krista Fischer - University of Tartu
Aaron R. Folsom - University of Minnesota
Melissa E. Garcia - NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA
Paolo Gasparini - Ist Ricovero & Cura Carattere Sci Materno Infanti, Inst Maternal & Child Hlth, Trieste, Italy
Christian Gieger - Helmholtz Zentrum München
Nicole Glazer - Boston University
Diederick E. Grobbee - College Station Medical Center
Per Hall - Karolinska Institutet
Toomas Haller - University of Tartu
Susan E. Hankinson - Harvard University
Merli Hass - University of Tartu
Caroline Hayward - University of Edinburgh
Andrew C. Heath - Washington Univ, St Louis, MO USA
Albert Hofman - Erasmus MC
Erik Ingelsson - Karolinska Institutet
A. Cecile J. W. Janssens - Erasmus MC
Andrew D. Johnson - Framingham Heart Study
David Karasik - Framingham Heart Study
Sharon L. R. Kardia - Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA
Jules Keyzer - Diagnost GP Lab Eindhoven, Eindhoven, Netherlands
Douglas P. Kiel - Framingham Heart Study
Ivana Kolcic - University of Split
Zoltan Kutalik - University of Lausanne
Jari Lahti - University of Helsinki
Sandra Lai - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
Triin Laisk - University of Tartu
Joop S. E. Laven - Erasmus MC
Debbie A. Lawlor - University of Bristol
Jianjun Liu - Genome Institute of Singapore
Lorna M. Lopez - University of Edinburgh
Yvonne V. Louwers - Erasmus MC
Patrik K. E. Magnusson - Karolinska Institutet
Mara Marongiu - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
Nicholas G. Martin
Irena Martinovic Klaric - Inst Migrat & Ethn Studies, Zagreb, Croatia
Corrado Masciullo - Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy
Barbara McKnight - University of Washington
Sarah E. Medland
David Melzer - University of Exeter
Vincent Mooser - GlaxoSmithKline
Pau Navarro - Mylan
Anne B. Newman - University of Pittsburgh
Dale R. Nyholt
N. Charlotte Onland-Moret - College Station Medical Center
Aarno Palotie - Wellcome Sanger Institute
Guillaume Pare - Brigham and Women's Hospital
Alex N. Parker - Amgen
Nancy L. Pedersen - Karolinska Institutet
Petra H. M. Peeters - College Station Medical Center
Giorgio Pistis - Mylan
Andrew S. Plump - Merck Res Lab, Rahway, NJ USA
Ozren Polasek - University of Split
Victor J. M. Pop - Tilburg University
Bruce M. Psaty - University of Washington
Katri Raikkonen - University of Helsinki
Emil Rehnberg - Karolinska Institutet
Jerome I. Rotter - College Station Medical Center
Igor Rudan - University of Split
Cinzia Sala - Mylan
Andres Salumets - University of Tartu
Angelo Scuteri - NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA
Andrew Singleton - NIA, Neurogenet Lab, Bethesda, MD 20892 USA
Jennifer A. Smith - Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA
Harold Snieder - University of Groningen
Nicole Soranzo - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Simon N. Stacey - deCODE Genet, Reykjavik, Iceland
John M. Starr - University of Edinburgh
Maria G. Stathopoulou - Harokopio University of Athens
Kathleen Stirrups - Wellcome Sanger Institute
Ronald P. Stolk - University of Groningen
Unnur Styrkarsdottir - deCODE Genet, Reykjavik, Iceland
Yan V. Sun - Emory University
Albert Tenesa - University of Edinburgh
Barbara Thorand - Helmholtz Zentrum München
Daniela Toniolo - Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy
Laufey Tryggvadottir - University of Iceland
Kim Tsui - Amgen Inc, Cambridge, MA USA
Sheila Ulivi - Ist Ricovero & Cura Carattere Sci Materno Infanti, Inst Maternal & Child Hlth, Trieste, Italy
Rob M. van Dam - Harvard University
Yvonne T. van der Schouw - College Station Medical Center
Carla H. van Gils - College Station Medical Center
Peter van Nierop - Municipal Hlth Serv Brabant Zuidoost, Helmond, Netherlands
Jacqueline M. Vink - University of Amsterdam
Peter M. Visscher - University of Edinburgh
Marlies Voorhuis - College Station Medical Center
Gerard Waeber - University of Lausanne
Henri Wallaschofski - University of Greifswald
H. Erich Wichmann - Helmholtz Zentrum München
Elisabeth Widen - University of Helsinki
Colette J. M. Wijnands-van Gent - POZOB Veldhoven, Veldhoven, Netherlands
Gonneke Willemsen - University of Amsterdam
James F. Wilson - University of Edinburgh
Bruce H. R. Wolffenbuttel - University of Groningen
Alan F. Wright - University of Edinburgh
Laura M. Yerges-Armstrong - Supreme Council Of Health
Tatijana Zemunik - University of Split
Lina Zgaga - University of Edinburgh
M. Carola Zillikens - Erasmus MC
Marek Zygmunt - University of Greifswald
Alice M. Arnold - University of Washington
Dorret I. Boomsma - University of Amsterdam
Julie E. Buring - Brigham and Women's Hospital
Laura Crisponi - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
Ellen W. Demerath - University of Minnesota
Vilmundur Gudnason - Iceland Heart Assoc, Kopavogur, Iceland
Tamara B. Harris - NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA
Frank B. Hu - Harvard University
David J. Hunter - Harvard University
Lenore J. Launer - NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA
Andres Metspalu - University of Tartu
Grant W. Montgomery
Ben A. Oostra - Erasmus MC
Paul M. Ridker - Brigham and Women's Hospital
Serena Sanna - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
David Schlessinger - NIA, Intramural Res Program, Baltimore, MD 21224 USA
Tim D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Kari Stefansson - deCODE Genet, Reykjavik, Iceland
Elizabeth A. Streeten - Supreme Council Of Health
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
Manuela Uda - CNR, Ist Ric Genet & Biomed, Cagliari, Italy
Andre G. Uitterlinden - Erasmus MC
Cornelia M. van Duijn - Netherlands Consortium Hlth Aging, Rotterdam, Netherlands
Henry Voelzke - University of Greifswald
Anna Murray - University of Exeter
Joanne M. Murabito - Boston University
Jenny A. Visser - Erasmus MC
Kathryn L. Lunetta - Boston University
LifeLines Cohort Study
Publication Details: Nature genetics, Vol.44(3), pp.260-U55
Publisher: Springer Nature
Number of pages: 11
Grant note: 263 MD9164 13; 263 MD821336 / NIMHD NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) P30DK072488 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) G0700704B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) BB/F019394/1 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) R01 AR041398; R01 AR041398-09 / NIAMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01MD009164 / National Institute on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) K05 AA017688 / NIAAA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) K05AA017688 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) CZB/4/710 / Chief Scientist Office N01HC035129 / DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) R01AR041398 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) N01 AG012109; N01 AG012100; R21 AG032598-01; N01 AG050002; R21 AG032598 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) MC_U127561128 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) U01HG004402 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) BB/F019394/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) P01 CA087969; R01 CA040356-15; U01 CA098233; R01 CA047988; U01 CA098233-01; P01 CA087969-12; R01 CA047988-09 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA047988 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01HL043851 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) UL1 TR000124 / NCATS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) P30 DK072488; P30 DK063491 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) ZIAAG007270 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) MC_PC_U127592696; MC_PC_U127561128; MC_U127561128; G0700704; MC_U127592696; G0600705 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission U01 HL084756-01; R01 HL043851-09; U01 HL072515; N01 HC025195; N01 HC085086; R01 HL087660; R01 HL087660-01; N01 HC035129; N01 HC055015; U01 HL072515-01; R01 HL105756; R01 HL105756-01; N02 HL64278; U01 HL084756 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R69/0208 / The Dunhill Medical Trust; Dunhill Medical Trust U01 HG004402-01; U01 HG004402 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
Identifiers: 9938498708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article