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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.
Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
| Title | Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Stolk, L, Perry, JRB, Chasman, DI, He, C, Mangino, M, Sulem, P, Barbalic, M, Broer, L, Byrne, EM, Ernst, F, Esko, T, Franceschini, N, Gudbjartsson, DF, Hottenga, J-J, Kraft, P, McArdle, PF, Porcu, E, Shin, S-Y, Smith, AV, van Wingerden, S, Zhai, G, Zhuang, WV, Albrecht, E, Alizadeh, BZ, Aspelund, T, Bandinelli, S, Lauc, LBarac, Beckmann, JS, Boban, M, Boerwinkle, E, Broekmans, FJ, Burri, A, Campbell, H, Chanock, SJ, Chen, C, Cornelis, MC, Corre, T, Coviello, AD, D'Adamo, P, Davies, G, de Faire, U, de Geus, EJC, Deary, IJ, Dedoussis, GVZ, Deloukas, P, Ebrahim, S, Eiriksdottir, G, Emilsson, V, Eriksson, JG, Fauser, BCJM, Ferreli, L, Ferrucci, L, Fischer, K, Folsom, AR, Garcia, ME, Gasparini, P, Gieger, C, Glazer, N, Grobbee, DE, Hall, P, Haller, T, Hankinson, SE, Hass, M, Hayward, C, Heath, AC, Hofman, A, Ingelsson, E, A Janssens, CJW, Johnson, AD, Karasik, D, Kardia, SLR, Keyzer, J, Kiel, DP, Kolcic, I, Kutalik, Z, Lahti, J, Lai, S, Laisk, T, Laven, JSE, Lawlor, DA, Liu, J, Lopez, LM, Louwers, YV, Magnusson, PKE, Marongiu, M, Martin, NG, Klaric, IMartinovic, Masciullo, C, McKnight, B, Medland, SE, Melzer, D, Mooser, V, Navarro, P, Newman, AB, Nyholt, DR, Onland-Moret, CN, Palotie, A, Paré, G, Parker, AN, Pedersen, NL, Peeters, PHM, Pistis, G, Plump, AS, Polasek, O, Pop, VJM, Psaty, BM, Räikkönen, K, Rehnberg, E, Rotter, JI, Rudan, I, Sala, C, Salumets, A, Scuteri, A, Singleton, A, Smith, JA, Snieder, H, Soranzo, N, Stacey, SN, Starr, JM, Stathopoulou, MG, Stirrups, K, Stolk, RP, Styrkarsdottir, U, Sun, YV, Tenesa, A, Thorand, B, Toniolo, D, Tryggvadottir, L, Tsui, K, Ulivi, S, van Dam, RM, van der Schouw, YT, van Gils, CH, van Nierop, P, Vink, JM, Visscher, PM, Voorhuis, M, Waeber, G, Wallaschofski, H, Wichmann, EH, Widen, E, van Gent, CJMWijnan, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wright, AF, Yerges-Armstrong, LM, Zemunik, T, Zgaga, L, Zillikens, CM, Zygmunt, M, Arnold, AM, Boomsma, DI, Buring, JE, Crisponi, L, Demerath, EW, Gudnason, V, Harris, TB, Hu, FB, Hunter, DJ, Launer, LJ, Metspalu, A, Montgomery, GW, Oostra, BA, Ridker, PM, Sanna, S, Schlessinger, D, Spector, TD, Stefansson, K, Streeten, EA, Thorsteinsdottir, U, Uda, M, Uitterlinden, AG, van Duijn, CM, Völzke, H, Murray, A, Murabito, JM, Visser, JA, Lunetta, KL |
| Corporate/Institutional Authors | LifeLines Cohort Study, |
| Journal | Nat Genet |
| Volume | 44 |
| Issue | 3 |
| Pagination | 260-8 |
| Date Published | 2012 Jan 22 |
| ISSN | 1546-1718 |
| Keywords | Age Factors, DNA Helicases, DNA Polymerase gamma, DNA Primase, DNA Repair, DNA Repair Enzymes, DNA-Directed DNA Polymerase, European Continental Ancestry Group, Exodeoxyribonucleases, Female, Genetic Loci, Genome-Wide Association Study, Humans, Immunity, Menopause, Polymorphism, Single Nucleotide, Proteins |
| Abstract | <p>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.</p> |
| DOI | 10.1038/ng.1051 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 22267201 |
| PubMed Central ID | PMC3288642 |
| Grant List | CZB/4/710 / / Chief Scientist Office / United Kingdom N01 HC085086 / HC / NHLBI NIH HHS / United States K05 AA017688 / AA / NIAAA NIH HHS / United States N01 AG012100 / AG / NIA NIH HHS / United States G0600705 / / Medical Research Council / United Kingdom R01 HL105756-01 / HL / NHLBI NIH HHS / United States U01 HG004402-01 / HG / NHGRI NIH HHS / United States P01 CA087969 / CA / NCI NIH HHS / United States R01 CA047988-09 / CA / NCI NIH HHS / United States R21 AG032598-01 / AG / NIA NIH HHS / United States R01 HL043851 / HL / NHLBI NIH HHS / United States R01 HL087660 / HL / NHLBI NIH HHS / United States MC_U127561128 / / Medical Research Council / United Kingdom R01 AR041398-09 / AR / NIAMS NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N02 HL64278 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States R01 HL087660-01 / HL / NHLBI NIH HHS / United States R01 AR041398 / AR / NIAMS NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States 263 MD821336 / MD / NIMHD NIH HHS / United States 263 MD9164 13 / MD / NIMHD NIH HHS / United States U01 HL084756 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 CA040356-15 / CA / NCI NIH HHS / United States P30 DK072488 / DK / NIDDK NIH HHS / United States MC_PC_U127592696 / / Medical Research Council / United Kingdom N01 AG050002 / AG / NIA NIH HHS / United States N01 AG012109 / AG / NIA NIH HHS / United States MC_PC_U127561128 / / Medical Research Council / United Kingdom U01 HL072515 / HL / NHLBI NIH HHS / United States R01 HL043851-09 / HL / NHLBI NIH HHS / United States U01 CA098233 / CA / NCI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States R01 CA047988 / CA / NCI NIH HHS / United States U01 HL072515-01 / HL / NHLBI NIH HHS / United States R21 AG032598 / AG / NIA NIH HHS / United States G0700704 / / Medical Research Council / United Kingdom BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom U01 CA098233-01 / CA / NCI NIH HHS / United States P01 CA087969-12 / CA / NCI NIH HHS / United States MC_U127592696 / / Medical Research Council / United Kingdom U01 HL084756-01 / HL / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R69/0208 / / The Dunhill Medical Trust / United Kingdom |