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Meta-Analysis
. 2010 Dec;42(12):1077-85.
doi: 10.1038/ng.714.

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

Cathy E Elks  1 , John R B Perry, Patrick Sulem, Daniel I Chasman, Nora Franceschini, Chunyan He, Kathryn L Lunetta, Jenny A Visser, Enda M Byrne, Diana L Cousminer, Daniel F Gudbjartsson, Tõnu Esko, Bjarke Feenstra, Jouke-Jan Hottenga, Daniel L Koller, Zoltán Kutalik, Peng Lin, Massimo Mangino, Mara Marongiu, Patrick F McArdle, Albert V Smith, Lisette Stolk, Sophie H van Wingerden, Jing Hua Zhao, Eva Albrecht, Tanguy Corre, Erik Ingelsson, Caroline Hayward, Patrik K E Magnusson, Erin N Smith, Shelia Ulivi, Nicole M Warrington, Lina Zgaga, Helen Alavere, Najaf Amin, Thor Aspelund, Stefania Bandinelli, Inês Barroso, Gerald S Berenson, Sven Bergmann, Hannah Blackburn, Eric Boerwinkle, Julie E Buring, Fabio Busonero, Harry Campbell, Stephen J Chanock, Wei Chen, Marilyn C Cornelis, David Couper, Andrea D Coviello, Pio d'Adamo, Ulf de Faire, Eco J C de Geus, Panos Deloukas, Angela Döring, George Davey Smith, Douglas F Easton, Gudny Eiriksdottir, Valur Emilsson, Johan Eriksson, Luigi Ferrucci, Aaron R Folsom, Tatiana Foroud, Melissa Garcia, Paolo Gasparini, Frank Geller, Christian Gieger; GIANT Consortium; Vilmundur Gudnason, Per Hall, Susan E Hankinson, Liana Ferreli, Andrew C Heath, Dena G Hernandez, Albert Hofman, Frank B Hu, Thomas Illig, Marjo-Riitta Järvelin, Andrew D Johnson, David Karasik, Kay-Tee Khaw, Douglas P Kiel, Tuomas O Kilpeläinen, Ivana Kolcic, Peter Kraft, Lenore J Launer, Joop S E Laven, Shengxu Li, Jianjun Liu, Daniel Levy, Nicholas G Martin, Wendy L McArdle, Mads Melbye, Vincent Mooser, Jeffrey C Murray, Sarah S Murray, Michael A Nalls, Pau Navarro, Mari Nelis, Andrew R Ness, Kate Northstone, Ben A Oostra, Munro Peacock, Lyle J Palmer, Aarno Palotie, Guillaume Paré, Alex N Parker, Nancy L Pedersen, Leena Peltonen, Craig E Pennell, Paul Pharoah, Ozren Polasek, Andrew S Plump, Anneli Pouta, Eleonora Porcu, Thorunn Rafnar, John P Rice, Susan M Ring, Fernando Rivadeneira, Igor Rudan, Cinzia Sala, Veikko Salomaa, Serena Sanna, David Schlessinger, Nicholas J Schork, Angelo Scuteri, Ayellet V Segrè, Alan R Shuldiner, Nicole Soranzo, Ulla Sovio, Sathanur R Srinivasan, David P Strachan, Mar-Liis Tammesoo, Emmi Tikkanen, Daniela Toniolo, Kim Tsui, Laufey Tryggvadottir, Jonathon Tyrer, Manuela Uda, Rob M van Dam, Joyce B J van Meurs, Peter Vollenweider, Gerard Waeber, Nicholas J Wareham, Dawn M Waterworth, Michael N Weedon, H Erich Wichmann, Gonneke Willemsen, James F Wilson, Alan F Wright, Lauren Young, Guangju Zhai, Wei Vivian Zhuang, Laura J Bierut, Dorret I Boomsma, Heather A Boyd, Laura Crisponi, Ellen W Demerath, Cornelia M van Duijn, Michael J Econs, Tamara B Harris, David J Hunter, Ruth J F Loos, Andres Metspalu, Grant W Montgomery, Paul M Ridker, Tim D Spector, Elizabeth A Streeten, Kari Stefansson, Unnur Thorsteinsdottir, André G Uitterlinden, Elisabeth Widen, Joanne M Murabito, Ken K Ong, Anna Murray
Affiliations
Meta-Analysis

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

Cathy E Elks et al. Nat Genet. 2010 Dec.

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 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 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.

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Figures

Fig. 1
Fig. 1
Flow diagram of the discovery and confirmation of novel loci for age at menarche. GC: genomic control.
See this image and copyright information in PMC

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