Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche

被引：158

作者：

Sulem, Patrick ^{[11
]}

Gudbjartsson, Daniel F. ^{[11
]}

Rafnar, Thorunn ^{[11
]}

Holm, Hilma ^{[1
,11
]}

Olafsdottir, Elinborg J. ^{[2
]}

Olafsdottir, Gudridur H. ^{[2
]}

Jonsson, Thorvaldur ^{[3
]}

Alexandersen, Peter ^{[4
]}

Feenstra, Bjarke ^{[5
]}

Boyd, Heather A. ^{[5
]}

Aben, Katja K. ^{[6
]}

Verbeek, Andre L. M. ^{[7
]}

Roeleveld, Nel ^{[7
]}

Jonasdottir, Aslaug ^{[11
]}

Styrkarsdottir, Unnur ^{[11
]}

Steinthorsdottir, Valgerdur ^{[11
]}

Karason, Ari ^{[11
]}

Stacey, Simon N. ^{[11
]}

Gudmundsson, Julius ^{[11
]}

Jakobsdottir, Margret ^{[11
]}

Thorleifsson, Gudmar ^{[11
]}

Hardarson, Gudmundur ^{[11
]}

Gulcher, Jeffrey ^{[11
]}

Kong, Augustine ^{[11
]}

Kiemeney, Lambertus A. ^{[6
,7
,8
]}

Melbye, Mads ^{[5
]}

Christiansen, Claus ^{[9
]}

Tryggvadottir, Laufey ^{[2
]}

Thorsteinsdottir, Unnur ^{[10
,11
]}

Stefansson, Kari ^{[10
]}

机构：

[1] Emory Univ, Sch Med, Div Cardiol, Dept Internal Med, Atlanta, GA 30322 USA

[2] Iceland Canc Registry, Reykjavik, Iceland

[3] Univ Hosp, Dept Surg, Reykjavik, Iceland

[4] Ctr Clin & Basic Res AS, Ballerup, Denmark

[5] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[6] Comprehens Canc Ctr E, Nijmegen, Netherlands

[7] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6525 ED Nijmegen, Netherlands

[8] Radboud Univ Nijmegen, Dept Urol, NL-6525 ED Nijmegen, Netherlands

[9] Nord Biosci AS, Herlev, Denmark

[10] Univ Iceland, Fac Med, Reykjavik, Iceland

[11] deCODE Genet, Reykjavik, Iceland

来源：

NATURE GENETICS | 2009年 / 41卷 / 06期

关键词：

INTERNATIONAL VARIABILITY; ADULT OBESITY; TWIN FAMILIES; HEIGHT; RISK; CANCER; COHORT; LOCI; MENOPAUSE; CHILDHOOD;

D O I：

10.1038/ng.383

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Earlier menarche correlates with shorter adult height(1) and higher childhood body fat(2). We conducted a genome-wide association study of age at menarche (AAM) on 15,297 Icelandic women. Combined analysis with replication sets from Iceland, Denmark and the Netherlands (N = 10,040) yielded a significant association between rs314280[T] on 6q21, near the LIN28B gene, and AAM (effect = 1.2 months later per allele; P = 1.8 x 10(-14)). A second SNP within the same linkage disequilibrium (LD) block, rs314277, splits rs314280[T] into two haplotypes with different effects (0.9 months and 1.9 months per allele). These variants have been associated with greater adult height(3,4). The association with adult height did not account for the association with AAM or vice versa. Other variants, previously associated with height(3-5), did not associate significantly with AAM. Given the link between body fat and AAM, we also assessed 11 variants recently associated with higher body mass index (BMI)(6-11) and 5 of those associated with earlier AAM.

引用

页码：734 / 738

页数：5

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