Genetic variation in LIN28B is associated with the timing of puberty.
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.
Ong
Ken K
KK
Medical Research Council (MRC) Epidemiology Unit, Addenbrooke's Hospital, Cambridge, UK. ken.ong@mrc-epid.cam.ac.uk
Elks
Cathy E
CE
Li
Shengxu
S
Zhao
Jing Hua
JH
Luan
Jian'an
J
Andersen
Lars B
LB
Bingham
Sheila A
SA
Brage
Soren
S
Smith
George Davey
GD
Ekelund
Ulf
U
Gillson
Christopher J
CJ
Glaser
Beate
B
Golding
Jean
J
Hardy
Rebecca
R
Khaw
Kay-Tee
KT
Kuh
Diana
D
Luben
Robert
R
Marcus
Michele
M
McGeehin
Michael A
MA
Ness
Andrew R
AR
Northstone
Kate
K
Ring
Susan M
SM
Rubin
Carol
C
Sims
Matthew A
MA
Song
Kijoung
K
Strachan
David P
DP
Vollenweider
Peter
P
Waeber
Gerard
G
Waterworth
Dawn M
DM
Wong
Andrew
A
Deloukas
Panagiotis
P
Barroso
Inês
I
Mooser
Vincent
V
Loos
Ruth J
RJ
Wareham
Nicholas J
NJ
D000328:Adult; D001827:Body Height; D001940:Breast / Q000254:growth & development; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005835:Genitalia / Q000254:growth & development / Q000502:physiology; D006197:Hair / Q000254:growth & development / Q000502:physiology; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D035683:MicroRNAs / Q000235:genetics; D009035:Mothers; D020641:Polymorphism, Single Nucleotide; D011627:Puberty / Q000235:genetics*; D016601:RNA-Binding Proteins; D012044:Regression Analysis
D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins