Genetic variation in LIN28B is associated with the timing of puberty

KK Ong, CE Elks, S Li, JH Zhao, J Luan, LB Andersen, S A Bingham, S Brage, G Davey Smith, U Ekelund, CJ Gillson, MUB Glaser, J Golding, R Hardy, KT Khaw, D Kuh, R Luben, M Marcus, MA McGeehin, A NessK Northstone, SM Ring, C Rubin, MA Sims, K Song, DP Strachan, P Vollenweider, G Waeber, DM Waterworth, A Wong, P Deloukas, I Barroso, V Mooser, RJ Loos, NJ Wareham

Research output: Contribution to journalArticle (Academic Journal)peer-review

255 Citations (Scopus)

Abstract

The timing of puberty is highly variable1. 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 times 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 times 10-10; combined P = 3.6 times 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 times 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 processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.
Translated title of the contributionGenetic variation in LIN28B is associated with the timing of puberty
Original languageEnglish
Pages (from-to)729-733
JournalNature Genetics
Volume41
DOIs
Publication statusPublished - 2009

Bibliographical note

Publisher: Nature Pub. Co

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