Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

被引：394

作者：

Elks, Cathy E. ^{[2
,7
]}

Perry, John R. B. ^{[3
,7
]}

Sulem, Patrick ^{[4
,7
]}

Chasman, Daniel I. ^{[5
,6
]}

Franceschini, Nora ^{[7
]}

He, Chunyan ^{[8
,9
]}

Lunetta, Kathryn L. ^{[1
,10
]}

Visser, Jenny A. ^{[11
]}

Byrne, Enda M. ^{[12
,13
]}

Cousminer, Diana L. ^{[14
]}

Gudbjartsson, Daniel F. ^{[4
]}

Esko, Tonu ^{[15
,16
,17
]}

Feenstra, Bjarke ^{[18
]}

Hottenga, Jouke-Jan ^{[19
]}

Koller, Daniel L. ^{[20
]}

Kutalik, Zoltan ^{[21
,22
]}

Lin, Peng ^{[23
]}

Mangino, Massimo ^{[24
]}

Marongiu, Mara ^{[25
]}

McArdle, Patrick F. ^{[26
]}

Smith, Albert V. ^{[27
,28
]}

Stolk, Lisette ^{[11
,29
]}

Van Wingerden, Sophie H. ^{[30
]}

Zhao, Jing Hua ^{[2
]}

Albrecht, Eva ^{[31
]}

Corre, Tanguy ^{[32
]}

Ingelsson, Erik ^{[33
]}

Hayward, Caroline ^{[34
]}

Magnusson, Patrik K. E. ^{[33
]}

Smith, Erin N. ^{[35
,36
,37
]}

Ulivi, Shelia ^{[38
]}

Warrington, Nicole M. ^{[39
]}

Zgaga, Lina ^{[40
]}

Alavere, Helen ^{[15
]}

Amin, Najaf ^{[30
]}

Aspelund, Thor ^{[27
,28
]}

Bandinelli, Stefania ^{[41
]}

Barroso, Ines ^{[42
]}

Berenson, Gerald S. ^{[43
]}

Bergmann, Sven ^{[21
,22
]}

Blackburn, Hannah ^{[42
]}

Boerwinkle, Eric ^{[44
]}

Buring, Julie E. ^{[5
,6
,45
]}

Busonero, Fabio ^{[25
]}

Campbell, Harry ^{[40
]}

Chanock, Stephen J. ^{[46
]}

Chen, Wei ^{[43
]}

Cornelis, Marilyn C. ^{[47
]}

Couper, David ^{[48
]}

Coviello, Andrea D. ^{[49
]}

机构：

[1] NHLBI, Framingham Heart Study, Framingham, MA USA

[2] Addenbrookes Hosp, Epidemiol Unit, MRC, Inst Metab Sci, Cambridge, England

[3] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England

[4] deCODE Genet, Reykjavik, Iceland

[5] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Boston, MA USA

[7] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA

[8] Indiana Univ, Sch Med, Dept Publ Hlth, Indiana, PA USA

[9] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indiana, PA USA

[10] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[11] Erasmus Med Ctr MC, Dept Internal Med, Rotterdam, Netherlands

[12] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[13] Univ Queensland, Brisbane, Qld, Australia

[14] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland

[15] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[16] Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-50090 Tartu, Estonia

[17] Estonian Bioctr, Genotyping Core Facil, Tartu, Estonia

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

[19] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[20] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[21] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[22] Swiss Inst Bioinformat, Lausanne, Switzerland

[23] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[24] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[25] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy

[26] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[27] Iceland Heart Assoc, Kopavogur, Iceland

[28] Univ Iceland, Reykjavik, Iceland

[29] Netherlands Consortium Healthy Aging, Rotterdam, Netherlands

[30] Erasmus Univ, Dept Epidemiol, Med Ctr, Genet Epidemiol Unit, Rotterdam, Netherlands

[31] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[32] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy

[33] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[34] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[35] Scripps Genom Med, La Jolla, CA USA

[36] Scripps Translat Sci Inst, La Jolla, CA USA

[37] Scripps Res Inst, La Jolla, CA 92037 USA

[38] Univ Trieste, Dept Reprod Sci & Dev, Trieste, Italy

[39] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia

[40] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[41] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy

[42] Wellcome Trust Sanger Inst, Cambridge, England

[43] Tulane Univ, New Orleans, LA 70118 USA

[44] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA

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

[46] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[47] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[48] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA

[49] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med Prevent Med & Endocrinol, Boston, MA 02118 USA

[50] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden

来源：

NATURE GENETICS | 2010年 / 42卷 / 12期

基金：

英国医学研究理事会; 芬兰科学院; 瑞士国家科学基金会; 瑞典研究理事会; 美国国家卫生研究院; 澳大利亚研究理事会; 加拿大健康研究院; 新加坡国家研究基金会; 英国惠康基金;

关键词：

FOLLICLE-STIMULATING-HORMONE; ENERGY-BALANCE; SEQUENCE VARIANTS; INHIBIN-B; PUBERTY; WOMEN; GIRLS; GENE; HERITABILITY; CHILDHOOD;

D O I：

10.1038/ng.714

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 x 10(-60)) and 9q31.2 (P = 2.2 x 10(-33)), we identified 30 new menarche loci (all P < 5 x 10(-8)) and found suggestive evidence for a further 10 loci (P < 1.9 x 10(-6)). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

引用

页码：1077 / U73

页数：11

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