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


    Stolk, Lisette, Perry, John R B, Chasman, Daniel I, He, Chunyan, Mangino, Massimo, Sulem, Patrick, Barbalic, Maja, Broer, Linda, Byrne, Enda M, Ernst, Florian, Esko, Tõnu, Franceschini, Nora, Gudbjartsson, Daniel F, Hottenga, Jouke-Jan, Kraft, Peter, McArdle, Patrick F, Porcu, Eleonora, Shin, So-Youn, Smith, Albert V, van Wingerden, Sophie, Zhai, Guangju, Zhuang, Wei V, Albrecht, Eva, Alizadeh, Behrooz Z, Aspelund, Thor, Bandinelli, Stefania, Lauc, Lovorka Barac, Beckmann, Jacques S, Boban, Mladen, Boerwinkle, Eric, Broekmans, Frank J, Burri, Andrea, Campbell, Harry, Chanock, Stephen J, Chen, Constance, Cornelis, Marilyn C, Corre, Tanguy, Coviello, Andrea D, d'Adamo, Pio, Davies, Gail, de Faire, Ulf, de Geus, Eco J C, Deary, Ian J, Dedoussis, George V Z, Deloukas, Panagiotis, Ebrahim, Shah, Eiriksdottir, Gudny, Emilsson, Valur, Eriksson, Johan G, Fauser, Bart C J M, Ferreli, Liana, Ferrucci, Luigi, Fischer, Krista, Folsom, Aaron R, Garcia, Melissa E, Gasparini, Paolo, Gieger, Christian, Glazer, Nicole, Grobbee, Diederick E, Hall, Per, Haller, Toomas, Hankinson, Susan E, Hass, Merli, Hayward, Caroline, Heath, Andrew C, Hofman, Albert, Ingelsson, Erik, Janssens, A Cecile J W, Johnson, Andrew D, Karasik, David, Kardia, Sharon L R, Keyzer, Jules, Kiel, Douglas P, Kolcic, Ivana, Kutalik, Zoltán, Lahti, Jari, Lai, Sandra, Laisk, Triin, Laven, Joop S E, Lawlor, Debbie A, Liu, Jianjun, Lopez, Lorna M., Louwers, Yvonne V, Magnusson, Patrik K E, Marongiu, Mara, Martin, Nicholas G, Klaric, Irena Martinovic, Masciullo, Corrado, McKnight, Barbara, Medland, Sarah E, Melzer, David, Mooser, Vincent, Navarro, Pau, Newman, Anne B, Nyholt, Dale R, Onland-Moret, N Charlotte, Palotie, Aarno, Paré, Guillaume, Parker, Alex N, Pedersen, Nancy L, Peeters, Petra H M, Pistis, Giorgio, Plump, Andrew S, Polasek, Ozren, Pop, Victor J M, Psaty, Bruce M, Räikkönen, Katri, Rehnberg, Emil, Rotter, Jerome I, Rudan, Igor, Sala, Cinzia, Salumets, Andres, Scuteri, Angelo, Singleton, Andrew, Smith, Jennifer A, Snieder, Harold, Soranzo, Nicole, Stacey, Simon N, Starr, John M, Stathopoulou, Maria G, Stirrups, Kathleen, Stolk, Ronald P, Styrkarsdottir, Unnur, Sun, Yan V, Tenesa, Albert, Thorand, Barbara, Toniolo, Daniela, Tryggvadottir, Laufey, Tsui, Kim, Ulivi, Sheila, van Dam, Rob M, van der Schouw, Yvonne T, van Gils, Carla H, van Nierop, Peter, Vink, Jacqueline M, Visscher, Peter M, Voorhuis, Marlies, Waeber, Gérard, Wallaschofski, Henri, Wichmann, H Erich, Widen, Elisabeth, Wijnands-van Gent, Colette J M, Willemsen, Gonneke, Wilson, James F, Wolffenbuttel, Bruce H R, Wright, Alan F, Yerges-Armstrong, Laura M, Zemunik, Tatijana, Zgaga, Lina, Zillikens, M Carola, Zygmunt, Marek, Study, The LifeLines Cohort, Arnold, Alice M, Boomsma, Dorret I, Buring, Julie E, Crisponi, Laura, Demerath, Ellen W, Gudnason, Vilmundur, Harris, Tamara B, Hu, Frank B, Hunter, David J, Launer, Lenore J, Metspalu, Andres, Montgomery, Grant W, Oostra, Ben A, Ridker, Paul M, Sanna, Serena, Schlessinger, David, Spector, Tim D, Stefansson, Kari, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, Uda, Manuela, Uitterlinden, André G, van Duijn, Cornelia M, Völzke, Henry, Murray, Anna, Murabito, Joanne M, Visser, Jenny A and Lunetta, Kathryn L (2012) Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nature Genetics, 44 (3). pp. 260-268. ISSN 1061-4036

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    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-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
    Item Type: Article
    Keywords: Meta-analyses; identify; 13 loci; age; menopause; highlight DNA repair; immune pathways;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17331
    Identification Number: 10.1038/ng.1051
    Depositing User: Lorna Lopez
    Date Deposited: 19 Jun 2023 10:56
    Journal or Publication Title: Nature Genetics
    Publisher: Nature Research
    Refereed: Yes
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17331
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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