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

Cathy E Elks, 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, GIANT Consortium, Jouke-Jan Hottenga, Daniel L Koller, Zoltán Kutalik, Peng Lin, Massimo Mangino, Mara MarongiuPatrick 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, Albert Hofman, Peter Kraft, Joop S E Laven, Ben A Oostra, Fernando Rivadeneira, Joyce B J van Meurs, Cornelia M van Duijn, André G Uitterlinden

Research output: Contribution to journalArticleAcademicpeer-review

420 Citations (Scopus)

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 languageEnglish
Pages (from-to)1077-1085
Number of pages9
JournalNature Genetics
Volume42
Issue number12
DOIs
Publication statusPublished - Dec 2010

Research programs

  • EMC MM-01-39-02
  • EMC MM-01-39-04
  • EMC MM-01-52-07

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