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


Elks, CE; Perry, JR; Sulem, P; Chasman, DI; Franceschini, N; He, C; Lunetta, KL; Visser, JA; Byrne, EM; Cousminer, DL; Gudbjartsson, DF; Esko, T; Feenstra, B; Hottenga, JJ; Koller, DL; Kutalik, Z; Lin, P; Mangino, M; Marongiu, M; McArdle, PF; Smith, AV; Stolk, L; van Wingerden, SH; Zhao, JH; Albrecht, E; Corre, T; Ingelsson, E; Hayward, C; Magnusson, PK; Smith, EN; Ulivi, S; Warrington, NM; Zgaga, L; Alavere, H; Amin, N; Aspelund, T; Bandinelli, S; Barroso, I; Berenson, GS; Bergmann, S; Blackburn, H; Boerwinkle, E; Buring, JE; Busonero, F; Campbell, H; Chanock, SJ; Chen, W; Cornelis, MC; Couper, D; Coviello, AD; D'Adamo, P; de Faire, U; de Geus, EJ; Deloukas, P; Doring, A; Smith, GD; Easton, DF; Eiriksdottir, G; Emilsson, V; Eriksson, J; Ferrucci, L; Folsom, AR; Foroud, T; Garcia, M; Gasparini, P; Geller, F; Gieger, C; Gudnason, V; Hall, P; Hankinson, SE; Ferreli, L; Heath, AC; Hernandez, DG; Hofman, A; Hu, FB; Illig, T; Jarvelin, MR; Johnson, AD; Karasik, D; Khaw, KT; Kiel, DP; Kilpelainen, TO; Kolcic, I; Kraft, P; Launer, LJ; Laven, JS; LI, S; Liu, J; Levy, D; Martin, NG; McArdle, WL; Melbye, M; Mooser, V; Murray, JC; Murray, SS; Nalls, MA; Navarro, P; Nelis, M; Ness, AR; Northstone, K; Oostra, BA; Peacock, M; Palmer, LJ; Palotie, A; Pare, G; Parker, AN; Pedersen, NL; Peltonen, L; Pennell, CE; Pharoah, P; Polasek, O; Plump, AS; Pouta, A; Porcu, E; Rafnar, T; Rice, JP; Ring, SM; Rivadeneira, F; Rudan, I; Sala, C; Salomaa, V; Sanna, S; Schlessinger, D; Schork, NJ; Scuteri, A; Segre, AV; Shuldiner, AR; Soranzo, N; Sovio, U; Srinivasan, SR; Strachan, DP; Tammesoo, ML; Tikkanen, E; Toniolo, D; Tsui, K; Tryggvadottir, L; Tyrer, J; Uda, M; van Dam, RM; van Meurs, JB; Vollenweider, P; Waeber, G; Wareham, NJ; Waterworth, DM; Weedon, MN; Wichmann, HE; Willemsen, G; Wilson, JF; Wright, AF; Young, L; Zhai, G; Zhuang, WV; Bierut, LJ; Boomsma, DI; Boyd, HA; Crisponi, L; Demerath, EW; van Duijn, CM; Econs, MJ; Harris, TB; Hunter, DJ; Loos, RJ; Metspalu, A; Montgomery, GW; Ridker, PM; Spector, TD; Streeten, EA; Stefansson, K; Thorsteinsdottir, U; Uitterlinden, AG; Widen, E; Murabito, JM; Ong, KK; Murray, A; (2010) Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature genetics, 42 (12). pp. 1077-85. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.714

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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) and 9q31.2 (P = 2.2 x 10(3)(3)), we identified 30 new menarche loci (all P < 5 x 10) and found suggestive evidence for a further 10 loci (P < 1.9 x 10). 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.

Item Type: Article
Keywords: Adolescent, Aging/*physiology, Body Height/genetics, Body Size/genetics, Child, DNA Copy Number Variations/genetics, Female, Genetic Loci/*genetics, Genetic Predisposition to Disease, *Genome-Wide Association Study, Humans, Inheritance Patterns/genetics, Menarche/*genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Reproducibility of Results, Time Factors, Adolescent, Aging, physiology, Body Height, genetics, Body Size, genetics, Child, DNA Copy Number Variations, genetics, Female, Genetic Loci, genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inheritance Patterns, genetics, Menarche, genetics, Obesity, genetics, Polymorphism, Single Nucleotide, genetics, Quantitative Trait Loci, genetics, Reproducibility of Results, Time Factors
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 21102462
Web of Science ID: 284578800010
URI: http://researchonline.lshtm.ac.uk/id/eprint/1320

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