title: Genetic variation in LIN28B is associated with the timing of puberty.
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.
authors.affiliation: Medical Research Council (MRC) Epidemiology Unit, Addenbrooke's Hospital, Cambridge, UK. ken.ong@mrc-epid.cam.ac.uk
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Elks
authors.forename: Shengxu
authors.initials: S
authors.lastname: Li
authors.forename: Jing Hua
authors.initials: JH
authors.lastname: Zhao
authors.forename: Jian'an
authors.initials: J
authors.lastname: Luan
authors.forename: Lars B
authors.initials: LB
authors.lastname: Andersen
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
authors.forename: Soren
authors.initials: S
authors.lastname: Brage
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Ulf
authors.initials: U
authors.lastname: Ekelund
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gillson
authors.forename: Beate
authors.initials: B
authors.lastname: Glaser
authors.forename: Jean
authors.initials: J
authors.lastname: Golding
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.forename: Robert
authors.initials: R
authors.lastname: Luben
authors.forename: Michele
authors.initials: M
authors.lastname: Marcus
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGeehin
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ness
authors.forename: Kate
authors.initials: K
authors.lastname: Northstone
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Carol
authors.initials: C
authors.lastname: Rubin
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sims
authors.forename: Kijoung
authors.initials: K
authors.lastname: Song
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Gerard
authors.initials: G
authors.lastname: Waeber
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Waterworth
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Deloukas
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Loos
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins