Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations

被引：302

作者：

Hayes, M. Geoffrey ^{[1
,2
,3
]}

Urbanek, Margrit ^{[1
,2
]}

Ehrmann, David A. ^{[4
]}

Armstrong, Loren L. ^{[1
]}

Lee, Ji Young ^{[1
]}

Sisk, Ryan ^{[1
]}

Karaderi, Tugce ^{[5
]}

Barber, Thomas M. ^{[6
]}

McCarthy, Mark I. ^{[5
,7
,8
]}

Franks, Stephen ^{[9
]}

Lindgren, Cecilia M. ^{[5
,10
]}

Welt, Corrine K. ^{[11
]}

Diamanti-Kandarakis, Evanthia ^{[12
]}

Panidis, Dimitrios ^{[13
]}

Goodarzi, Mark O. ^{[14
]}

Azziz, Ricardo ^{[15
,16
]}

Zhang, Yi ^{[17
,18
]}

James, Roland G. ^{[17
,18
]}

Olivier, Michael ^{[19
]}

Kissebah, Ahmed H. ^{[17
,18
]}

Stener-Victorin, Elisabet ^{[20
]}

Legro, Richard S. ^{[21
]}

Dunaif, Andrea ^{[1
,2
]}

机构：

[1] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA

[2] Northwestern Univ, Ctr Genet Med, Feinberg Sch Med, Chicago, IL 60611 USA

[3] Northwestern Univ, Dept Anthropol, Evanston, IL 60208 USA

[4] Univ Chicago, Sect Endocrinol Diabet & Metab, Chicago, IL 60637 USA

[5] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[6] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England

[7] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England

[8] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Headington OX3 7LE, England

[9] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Inst Reprod & Dev Biol, London W12 0NN, England

[10] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA

[11] Univ Utah, Div Endocrinol Metab & Diabet, Salt Lake City, UT 84112 USA

[12] Univ Athens, Sch Med, Endocrinol & Metab, GR-11527 Athens, Greece

[13] Aristotle Univ Thessaloniki, Dept Obstet & Gynecol 2, Div Endocrinol & Human Reprod, Thessaloniki 54124, Greece

[14] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA

[15] Georgia Regents Univ, Med Coll Georgia, Dept Obstet & Gynecol, Augusta, GA 30912 USA

[16] Georgia Regents Univ, Med Coll Georgia, Dept Med, Augusta, GA 30912 USA

[17] Med Coll Wisconsin, Dept Med, TOPS Obes & Metab Res Ctr, Milwaukee, WI 53226 USA

[18] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA

[19] Texas Biomed Res Inst, Dept Genet, San Antonio, TX 78256 USA

[20] Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden

[21] Penn State Coll Med, Dept Obstet & Gynecol, Hershey, PA 17033 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

美国国家卫生研究院; 英国惠康基金;

关键词：

SYNDROME PCOS; SUSCEPTIBILITY LOCI; CHROMOSOME; 2P16.3; ANDROGEN EXCESS; QUALITY-CONTROL; EMERGE NETWORK; WOMEN; VARIANTS; IDENTIFICATION; IMPUTATION;

D O I：

10.1038/ncomms8502

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：

Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p32.1 and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.

引用

页数：12

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