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

M. Geoffrey Hayes, Margrit Urbanek, David A. Ehrmann, Loren L. Armstrong, Ji Young Lee, Ryan Sisk, Tugce Karaderi, Thomas M. Barber, Mark I. McCarthy, Stephen Franks, Cecilia M. Lindgren, Corrine K. Welt, Evanthia Diamanti-Kandarakis, Dimitrios Panidis, Mark O. Goodarzi, Ricardo Azziz, Yi Zhang, Roland G. James, Michael Olivier, Ahmed H. KissebahElisabet Stener-Victorin, Richard S. Legro, Andrea Dunaif, Ruben Alvero, Huiman X. Barnhart, Valerie Baker, Kurt T. Barnhart, G. Wright Bates, Robert G. Brzyski, Bruce R. Carr, Sandra A. Carson, Peter Casson, Nicholas A. Cataldo, Gregory Christman, Christos Coutifaris, Michael Peter Diamond, Esther Eisenberg, Gabriella G. Gosman, Linda C. Giudice, Daniel J. Haisenleder, Hao Huang, Stephen A. Krawetz, Scott Lucidi, Peter G. McGovern, Evan R. Myers, John E. Nestler, Dana Ohl, Nanette Santoro, William D. Schlaff, Peter Snyder, Michael P. Steinkampf, J. C. Trussell, Rebecca Usadi, Qingshang Yan, Heping Zhang

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number7502
JournalNature Communications
Volume6
DOIs
StatePublished - Aug 18 2015

Fingerprint

ovaries
secretions
hormones
genome
Polycystic Ovary Syndrome
Follicle Stimulating Hormone
Luteinizing Hormone
Gonadotropins
loci
Genes
Genome
Population
Androgens
Health
Hormones
Insulin
Glucose
Defects
Peptides
etiology

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. / Hayes, M. Geoffrey; Urbanek, Margrit; Ehrmann, David A.; Armstrong, Loren L.; Lee, Ji Young; Sisk, Ryan; Karaderi, Tugce; Barber, Thomas M.; McCarthy, Mark I.; Franks, Stephen; Lindgren, Cecilia M.; Welt, Corrine K.; Diamanti-Kandarakis, Evanthia; Panidis, Dimitrios; Goodarzi, Mark O.; Azziz, Ricardo; Zhang, Yi; James, Roland G.; Olivier, Michael; Kissebah, Ahmed H.; Stener-Victorin, Elisabet; Legro, Richard S.; Dunaif, Andrea; Alvero, Ruben; Barnhart, Huiman X.; Baker, Valerie; Barnhart, Kurt T.; Bates, G. Wright; Brzyski, Robert G.; Carr, Bruce R.; Carson, Sandra A.; Casson, Peter; Cataldo, Nicholas A.; Christman, Gregory; Coutifaris, Christos; Diamond, Michael Peter; Eisenberg, Esther; Gosman, Gabriella G.; Giudice, Linda C.; Haisenleder, Daniel J.; Huang, Hao; Krawetz, Stephen A.; Lucidi, Scott; McGovern, Peter G.; Myers, Evan R.; Nestler, John E.; Ohl, Dana; Santoro, Nanette; Schlaff, William D.; Snyder, Peter; Steinkampf, Michael P.; Trussell, J. C.; Usadi, Rebecca; Yan, Qingshang; Zhang, Heping.

In: Nature Communications, Vol. 6, 7502, 18.08.2015.

Research output: Contribution to journalArticle

Hayes, MG, Urbanek, M, Ehrmann, DA, Armstrong, LL, Lee, JY, Sisk, R, Karaderi, T, Barber, TM, McCarthy, MI, Franks, S, Lindgren, CM, Welt, CK, Diamanti-Kandarakis, E, Panidis, D, Goodarzi, MO, Azziz, R, Zhang, Y, James, RG, Olivier, M, Kissebah, AH, Stener-Victorin, E, Legro, RS, Dunaif, A, Alvero, R, Barnhart, HX, Baker, V, Barnhart, KT, Bates, GW, Brzyski, RG, Carr, BR, Carson, SA, Casson, P, Cataldo, NA, Christman, G, Coutifaris, C, Diamond, MP, Eisenberg, E, Gosman, GG, Giudice, LC, Haisenleder, DJ, Huang, H, Krawetz, SA, Lucidi, S, McGovern, PG, Myers, ER, Nestler, JE, Ohl, D, Santoro, N, Schlaff, WD, Snyder, P, Steinkampf, MP, Trussell, JC, Usadi, R, Yan, Q & Zhang, H 2015, 'Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations', Nature Communications, vol. 6, 7502. https://doi.org/10.1038/ncomms8502
Hayes, M. Geoffrey ; Urbanek, Margrit ; Ehrmann, David A. ; Armstrong, Loren L. ; Lee, Ji Young ; Sisk, Ryan ; Karaderi, Tugce ; Barber, Thomas M. ; McCarthy, Mark I. ; Franks, Stephen ; Lindgren, Cecilia M. ; Welt, Corrine K. ; Diamanti-Kandarakis, Evanthia ; Panidis, Dimitrios ; Goodarzi, Mark O. ; Azziz, Ricardo ; Zhang, Yi ; James, Roland G. ; Olivier, Michael ; Kissebah, Ahmed H. ; Stener-Victorin, Elisabet ; Legro, Richard S. ; Dunaif, Andrea ; Alvero, Ruben ; Barnhart, Huiman X. ; Baker, Valerie ; Barnhart, Kurt T. ; Bates, G. Wright ; Brzyski, Robert G. ; Carr, Bruce R. ; Carson, Sandra A. ; Casson, Peter ; Cataldo, Nicholas A. ; Christman, Gregory ; Coutifaris, Christos ; Diamond, Michael Peter ; Eisenberg, Esther ; Gosman, Gabriella G. ; Giudice, Linda C. ; Haisenleder, Daniel J. ; Huang, Hao ; Krawetz, Stephen A. ; Lucidi, Scott ; McGovern, Peter G. ; Myers, Evan R. ; Nestler, John E. ; Ohl, Dana ; Santoro, Nanette ; Schlaff, William D. ; Snyder, Peter ; Steinkampf, Michael P. ; Trussell, J. C. ; Usadi, Rebecca ; Yan, Qingshang ; Zhang, Heping. / Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. In: Nature Communications. 2015 ; Vol. 6.
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abstract = "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.",
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AU - Lee, Ji Young

AU - Sisk, Ryan

AU - Karaderi, Tugce

AU - Barber, Thomas M.

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AU - Franks, Stephen

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AU - Kissebah, Ahmed H.

AU - Stener-Victorin, Elisabet

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AU - Dunaif, Andrea

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AU - Barnhart, Huiman X.

AU - Baker, Valerie

AU - Barnhart, Kurt T.

AU - Bates, G. Wright

AU - Brzyski, Robert G.

AU - Carr, Bruce R.

AU - Carson, Sandra A.

AU - Casson, Peter

AU - Cataldo, Nicholas A.

AU - Christman, Gregory

AU - Coutifaris, Christos

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AU - Eisenberg, Esther

AU - Gosman, Gabriella G.

AU - Giudice, Linda C.

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AU - Lucidi, Scott

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AU - Ohl, Dana

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AU - Schlaff, William D.

AU - Snyder, Peter

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AU - Yan, Qingshang

AU - Zhang, Heping

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AB - 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.

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