TY - JOUR
T1 - Genetic variation in LIN28B is associated with the timing of puberty
AU - Ong, KK
AU - Elks, CE
AU - Li, S
AU - Zhao, JH
AU - Luan, J
AU - Andersen, LB
AU - Bingham, S A
AU - Brage, S
AU - Davey Smith, G
AU - Ekelund, U
AU - Gillson, CJ
AU - Glaser, MUB
AU - Golding, J
AU - Hardy, R
AU - Khaw, KT
AU - Kuh, D
AU - Luben, R
AU - Marcus, M
AU - McGeehin, MA
AU - Ness, A
AU - Northstone, K
AU - Ring, SM
AU - Rubin, C
AU - Sims, MA
AU - Song, K
AU - Strachan, DP
AU - Vollenweider, P
AU - Waeber, G
AU - Waterworth, DM
AU - Wong, A
AU - Deloukas, P
AU - Barroso, I
AU - Mooser, V
AU - Loos, RJ
AU - Wareham, NJ
N1 - Publisher: Nature Pub. Co
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1038/ng.382
DO - 10.1038/ng.382
M3 - Article (Academic Journal)
C2 - 19448623
VL - 41
SP - 729
EP - 733
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -