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Nat Genet. 2009 Jun;41(6):729-33. doi: 10.1038/ng.382. Epub 2009 May 17.

Genetic variation in LIN28B is associated with the timing of puberty.

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  • 1Medical Research Council (MRC) Epidemiology Unit, Addenbrooke's Hospital, Cambridge, UK. ken.ong@mrc-epid.cam.ac.uk

Abstract

The timing of puberty is highly variable. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 × 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 × 10(-10); combined P = 3.6 × 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 × 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing, as the first genetic determinant regulating the timing of human pubertal growth and development.

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PMID:
19448623
[PubMed - indexed for MEDLINE]
PMCID:
PMC3000552
Free PMC Article

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