Shared genetic aetiology of puberty timing between sexes and with health-related outcomes

被引：83

作者：

Day, Felix R. ^{[1
]}

Bulik-Sullivan, Brendan ^{[2
,3
,4
]}

Hinds, David A. ^{[5
]}

Finucane, Hilary K. ^{[6
,7
]}

Murabito, Joanne M. ^{[8
,9
]}

Tung, Joyce Y. ^{[5
]}

Ong, Ken K. ^{[1
,10
]}

Perry, John R. B. ^{[1
]}

机构：

[1] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England

[2] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[4] Broad Inst, Med & Populat Genet, Cambridge, MA 02142 USA

[5] 23andMe Inc, Mountain View, CA 94041 USA

[6] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[7] MIT, Dept Math, Cambridge, MA 02139 USA

[8] NHLBIs & Boston Univ Framingham Heart Study, Framingham, MA 01702 USA

[9] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA

[10] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; BODY-MASS; AGE; LOCI; METAANALYSIS; MENARCHE; VARIANTS; OBESITY; LIN28B; MALES;

D O I：

10.1038/ncomms9842

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P = 2.7 x 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (P-heterogeneity = 1.6 x 10(-12)). We find five novel loci for puberty timing (P<5 x 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease.

引用

页数：6

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