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

TitleGenetic variation in LIN28B is associated with the timing of puberty.
Publication TypeJournal Article
Year of Publication2009
AuthorsOng, KK, Elks, CE, Li, S, Zhao, JHua, Luan, J'an, Andersen, LB, Bingham, SA, Brage, S, Smith, GDavey, Ekelund, U, Gillson, CJ, Glaser, B, Golding, J, Hardy, R, Khaw, K-T, Kuh, D, Luben, R, Marcus, M, McGeehin, MA, Ness, AR, Northstone, K, Ring, SM, Rubin, C, Sims, MA, Song, K, Strachan, DP, Vollenweider, P, Waeber, G, Waterworth, DM, Wong, A, Deloukas, P, Barroso, I, Mooser, V, Loos, RJ, Wareham, NJ
JournalNat Genet
Volume41
Issue6
Pagination729-33
Date Published2009 Jun
ISSN1546-1718
KeywordsAdult, Body Height, Breast, Chromosomes, Human, Pair 6, DNA-Binding Proteins, Female, Genitalia, Hair, Humans, Male, Meta-Analysis as Topic, MicroRNAs, Mothers, Polymorphism, Single Nucleotide, Puberty, Regression Analysis, RNA-Binding Proteins
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.

DOI10.1038/ng.382
Alternate JournalNat. Genet.
Citation Key10.1038/ng.382
PubMed ID19448623
PubMed Central IDPMC3000552
Grant ListG0401527(74922) / / Medical Research Council / United Kingdom
MC_U123092721 / / Medical Research Council / United Kingdom
MC_U105630924 / / Medical Research Council / United Kingdom
077011 / / Wellcome Trust / United Kingdom
MC_U106179473 / / Medical Research Council / United Kingdom
077016 / / Wellcome Trust / United Kingdom
73437 / / Medical Research Council / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom
MC_U123092720 / / Medical Research Council / United Kingdom
/ / Cancer Research UK / United Kingdom
MC_U106179472 / / Medical Research Council / United Kingdom
G0401527 / / Medical Research Council / United Kingdom
079996 / / Wellcome Trust / United Kingdom
U.1061.00.004(79472) / / Medical Research Council / United Kingdom
076467/Z/05/Z / / Wellcome Trust / United Kingdom
068545/Z/02 / / Wellcome Trust / United Kingdom
068049 / / Wellcome Trust / United Kingdom
U.1061.00.001 (79471) / / Medical Research Council / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
MC_U106188470 / / Medical Research Council / United Kingdom
077016/Z/05/Z / / Wellcome Trust / United Kingdom
G0000934 / / Medical Research Council / United Kingdom
G9815508 / / Medical Research Council / United Kingdom