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

Stolk, L., Perry, J. R., Chasman, D. I., He, C., Mangino, M., Sulem, P., Barbalic, M., Broer, L., Byrne, E. M., Ernst, F., Esko, T., Franceschini, N., Gudbjartsson, D. F., Hottenga, J. J., Kraft, P., McArdle, P. F., Porcu, E., Shin, S. Y., Smith, A. V., van Wingerden, S., Zhai, G., Zhuang, W. V., Albrecht, E., Alizadeh, B. Z., Aspelund, T., Bandinelli, S., Lauc, L. B., Beckmann, J. S., Boban, M., Boerwinkle, E., Broekmans, F. J., Burri, A., Campbell, H., Chanock, S. J., Chen, C., Cornelis, M. C., Corre, T., Coviello, A. D., d'Adamo, P., Davies, G., de Faire, U., de Geus, E. J., Deary, I. J., Dedoussis, G. V., Deloukas, P., Ebrahim, S., Eiriksdottir, G., Emilsson, V., Eriksson, J. G., Fauser, B. C., Ferreli, L., Ferrucci, L., Fischer, K., Folsom, A. R., Garcia, M. E., Gasparini, P., Gieger, C., Glazer, N., Grobbee, D. E., Hall, P., Haller, T., Hankinson, S. E., Hass, M., Hayward, C., Heath, A. C., Hofman, A., Ingelsson, E., Janssens, A. C., Johnson, A. D., Karasik, D., Kardia, S. L., Keyzer, J., Kiel, D. P., Kolcic, I., Kutalik, Z., Lahti, J., Lai, S., Laisk, T., Laven, J. S., Lawlor, D. A., Liu, J., Lopez, L. M., Louwers, Y. V., Magnusson, P. K., Marongiu, M., Martin, N. G., Klaric, I. M., Masciullo, C., McKnight, B., Medland, S. E., Melzer, D., Mooser, V., Navarro, P., Newman, A. B., Nyholt, D.R., Onland-Moret, N. C., Palotie, A., Pare, G., Parker, A. N., Pedersen, N. L., Peeters, P. H., Pistis, G., Plump, A. S., Polasek, O., Pop, V. J., Psaty, B. M., Raikkonen, K., Rehnberg, E., Rotter, J. I., Rudan, I., Sala, C., Salumets, A., Scuteri, A., Singleton, A., Smith, J. A., Snieder, H., Soranzo, N., Stacey, S. N., Starr, J. M., Stathopoulou, M. G., Stirrups, K., Stolk, R. P., Styrkarsdottir, U., Sun, Y. V., Tenesa, A., Thorand, B., Toniolo, D., Tryggvadottir, L., Tsui, K., Ulivi, S., van Dam, R. M., van der Schouw, Y. T., van Gils, C. H., van Nierop, P., Vink, J. M., Visscher, P. M., Voorhuis, M., Waeber, G., Wallaschofski, H., Wichmann, H. E., Widen, E., Wijnands-van Gent, C. J., Willemsen, G., Wilson, J. F., Wolffenbuttel, B. H., Wright, A. F., Yerges-Armstrong, L. M., Zemunik, T., Zgaga, L., Zillikens, M. C., Zygmunt, M., Study, T. L., Arnold, A. M., Boomsma, D. I., Buring, J. E., Crisponi, L., Demerath, E. W., Gudnason, V., Harris, T. B., Hu, F. B., Hunter, D. J., Launer, L. J., Metspalu, A., Montgomery, G. W., Oostra, B. A., Ridker, P. M., Sanna, S., Schlessinger, D., Spector, T. D., Stefansson, K., Streeten, E. A., Thorsteinsdottir, U., Uda, M., Uitterlinden, A. G., van Duijn, C. M., Volzke, H., Murray, A., Murabito, J. M., Visser, J. A., & Lunetta, K. 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.

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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-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

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ID Code: 91838
Item Type: Journal Article
Refereed: Yes
Keywords: Age Factors, DNA Helicases/genetics, DNA Primase/genetics, DNA Repair/*genetics, DNA Repair Enzymes/genetics, DNA-Directed DNA Polymerase/genetics, European Continental Ancestry Group/genetics, Exodeoxyribonucleases/genetics, Female, Genetic Loci/*genetics, Genome-Wide Association Study, Humans, Immunity/*genetics, Menopause/*genetics/physiology, Polymorphism, Single Nucleotide/*genetics, Proteins/genetics
DOI: 10.1038/ng.1051
ISSN: 1546-1718
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 14 Jan 2016 01:19
Last Modified: 18 Jan 2016 02:03

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