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

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

To identify novel loci for age at natural menopause, we performed a meta-analysis of 22 genome-wide association studies in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 new age at natural menopause loci ( P < 5 × 10 −8 )...

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Veröffentlicht in:Nature genetics 2012-01, Vol.44 (3), p.260-268
Hauptverfasser: Stolk, Lisette, Perry, John RB, 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, Patick 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 JC, Deary, Ian J, Dedoussis, George VZ, Deloukas, Panagiotis, Ebrahim, Shah, Eiriksdottir, Gudny, Emilsson, Valur, Eriksson, Johan G, Fauser, Bart CJM, 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 JW, Johnson, Andrew D, Karasik, David, Kardia, Sharon LR, Keyzer, Jules, Kiel, Douglas P, Kolcic, Ivana, Kutalik, Zoltán, Lahti, Jari, Lai, Sandra, Laisk, Triin, Laven, Joop SE, Lawlor, Debbie A, Liu, Jianjun, Lopez, Lorna M, Louwers, Yvonne V, Magnusson, Patrik KE, 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
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Sprache:eng
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Zusammenfassung:To identify novel loci for age at natural menopause, we performed a meta-analysis of 22 genome-wide association studies in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 new age at natural menopause loci ( P < 5 × 10 −8 ). The new loci included genes implicated in DNA repair ( EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG, PRIM1 ) and immune function ( IL11, NLRP11, BAT2 ). Gene-set enrichment pathway analyses using the full GWAS dataset identified exodeoxyribonuclease, NFκB signalling and mitochondrial dysfunction as biological processes related to timing of menopause.
ISSN:1061-4036
1546-1718
DOI:10.1038/ng.1051