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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.

Original publication

DOI

10.1038/ng.714

Type

Journal article

Journal

Nature genetics

Publication Date

12/2010

Volume

42

Pages

1077 - 1085

Addresses

Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

Keywords

GIANT Consortium, Humans, Obesity, Genetic Predisposition to Disease, Body Size, Body Height, Reproducibility of Results, Aging, Menarche, Inheritance Patterns, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Time Factors, Adolescent, Child, Female, Genome-Wide Association Study, Genetic Loci, DNA Copy Number Variations