Genetic variation in LIN28B is associated with the timing of puberty

被引：254

作者：

Ong, Ken K. ^{[1
,2
,3
]}

Elks, Cathy E. ^{[1
,2
]}

Li, Shengxu ^{[1
,2
]}

Zhao, Jing Hua ^{[1
,2
]}

Luan, Jian'an ^{[1
,2
]}

Andersen, Lars B. ^{[4
]}

Bingham, Sheila A. ^{[5
,6
]}

Brage, Soren ^{[1
,2
]}

Smith, George Davey ^{[7
]}

Ekelund, Ulf ^{[1
,2
,8
]}

Gillson, Christopher J. ^{[1
,2
]}

Glaser, Beate ^{[7
]}

Golding, Jean ^{[9
]}

Hardy, Rebecca ^{[10
]}

Khaw, Kay-Tee ^{[11
]}

Kuh, Diana ^{[10
]}

Luben, Robert ^{[11
]}

Marcus, Michele ^{[12
,13
,14
]}

McGeehin, Michael A. ^{[12
]}

Ness, Andrew R. ^{[15
]}

Northstone, Kate ^{[16
]}

Ring, Susan M. ^{[16
]}

Rubin, Carol ^{[12
]}

Sims, Matthew A. ^{[1
,2
]}

Song, Kijoung ^{[17
]}

Strachan, David P. ^{[18
]}

Vollenweider, Peter ^{[19
]}

Waeber, Gerard ^{[19
]}

Waterworth, Dawn M. ^{[17
]}

Wong, Andrew ^{[10
]}

Deloukas, Panagiotis ^{[20
]}

Barroso, Ines ^{[20
]}

Mooser, Vincent ^{[17
]}

Loos, Ruth J. ^{[1
,2
]}

Wareham, Nicholas J. ^{[1
,2
]}

机构：

[1] Addenbrookes Hosp, MRC, Epidemiol Unit, Cambridge, England

[2] Addenbrookes Hosp, Inst Metab Sci, Cambridge, England

[3] Univ Cambridge, Dept Paediat, Cambridge, England

[4] Univ So Denmark, Inst Sport Sci & Clin Biomech, Odense, Denmark

[5] MRC Dunn Human Nutr Unit, Cambridge, England

[6] MRC Ctr Nutr Epidemiol Canc Prevent & Survival, Cambridge, England

[7] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England

[8] Univ Orebro, Sch Med & Hlth Sci, Orebro, Sweden

[9] Univ Bristol, Dept Community Based Med, ALSPAC, Bristol, Avon, England

[10] MRC Unit Lifelong Hlth & Ageing, London, England

[11] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England

[12] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA

[13] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA

[14] Emory Univ, Rollins Sch Publ Hlth, Dept Environm & Occupat Hlth, Atlanta, GA 30322 USA

[15] Univ Bristol, Dept Oral & Dent Sci, Bristol, Avon, England

[16] Univ Bristol, Dept Social Med, ALSPAC, Bristol, Avon, England

[17] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA

[18] Univ London, Div Community Hlth Sci, London, England

[19] BH10 CHUV, Dept Internal Med, Lausanne, Switzerland

[20] Wellcome Trust Sanger Inst, Cambridge, England

来源：

NATURE GENETICS | 2009年 / 41卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

EPIC-NORFOLK; IDENTIFICATION; RISK; AGE;

D O I：

10.1038/ng.382

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The timing of puberty is highly variable(1). 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 x 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 x 10(-10); combined P = 3.6 x 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 x 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(2), as the first genetic determinant regulating the timing of human pubertal growth and development.

引用

页码：729 / 733

页数：5

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