Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

CE Elks, JRB Perry, P Sulem, DI Chasman, N Franceschini, CY He, KL Lunetta, JA Visser, EM Byrne, DL Cousminer, DF Gudbjartsson, T Esko, B Feenstra, JJ (Jouke Jan) Hottenga, DL Koller, Z Kutalik, P Lin, M Mangino, M Marongiu, PF McArdleAV Smith, Lisette Stolk, Sophie Wingerden, JH Zhao, E Albrecht, T Corre, E Ingelsson, C Hayward, PKE Magnusson, EN Smith, S Ulivi, NM Warrington, L Zgaga, H Alavere, Najaf Amin, T Aspelund, S Bandinelli, I Barroso, GS Berenson, S Bergmann, H Blackburn, E Boerwinkle, JE Buring, F Busonero, H Campbell, SJ Chanock, W Chen, MC Cornelis, D Couper, AD Coviello, P d'Adamo, U de Faire, EJC de Geus, P Deloukas, A Doring, GD Smith, DF Easton, G Eiriksdottir, V Emilsson, J Eriksson, L Ferrucci, AR Folsom, T Foroud, M Garcia, P Gasparini, F Geller, C Gieger, V Gudnason, P Hall, SE Hankinson, L Ferreli, AC Heath, DG Hernandez, Bert Hofman, FB Hu, T Illig, MR Jarvelin, AD Johnson, D Karasik, KT Khaw, DP Kiel, TO Kilpelainen, I Kolcic, P Kraft, LJ (Lenore) Launer, Joop Laven, SX Li, JJ Liu, D Levy, NG Martin, WL McArdle, M Melbye, V Mooser, JC Murray, SS Murray, MA Nalls, P Navarro, M Nelis, AR Ness, K Northstone, Ben Oostra, M Peacock, LJ Palmer, A Palotie, G Pare, AN Parker, NL Pedersen, L Peltonen, CE Pennell, P Pharoah, O Polasek, AS Plump, A Pouta, E Porcu, T Rafnar, JP Rice, SM Ring, Fernando Rivadeneira, I Rudan, C Sala, V Salomaa, S Sanna, D Schlessinger, NJ Schork, A Scuteri, AV Segre, AR Shuldiner, N Soranzo, U Sovio, SR (Sathanur) Srinivasan, DP Strachan, ML Tammesoo, E Tikkanen, D Toniolo, K Tsui, L Tryggvadottir, J Tyrer, M Uda, RM van Dam, Joyce van Meurs, P Vollenweider, G Waeber, NJ Wareham, DM Waterworth, MN Weedon, HE Wichmann, G Willemsen, JF Wilson, AF Wright, L Young, GJ Zhai, WV Zhuang, LJ Bierut, DI Boomsma, HA Boyd, L Crisponi, EW Demerath, Cornelia Duijn, MJ Econs, TB Harris, DJ Hunter, RJF Loos, A Metspalu, GW Montgomery, PM Ridker, TD Spector, EA Streeten, K Stefansson, U Thorsteinsdottir, André Uitterlinden, E Widen, JM Murabito, KK Ong, A Murray

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Abstract

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 x 10(-60)) and 9q31.2 (P = 2.2 x 10(-33)), we identified 30 new menarche loci (all P < 5 x 10(-8)) and found suggestive evidence for a further 10 loci (P < 1.9 x 10(-6)). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
Original languageUndefined/Unknown
Pages (from-to)1077-U73
JournalNature Genetics
Volume42
Issue number12
DOIs
Publication statusPublished - 2010

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