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

ABSTRACT: 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(-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-?B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

SUBMITTER: Stolk L

PROVIDER: S-EPMC3288642 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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

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

Nature genetics 20120122 3

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(-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 ...[more]

PMID: 22267201

Dataset Information

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

Publications

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

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