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. Kissebah; Elisabet 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 P. 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

doi:10.1038/ncomms8502

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 P. 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

^*Corresponding author for this work

170 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 language	English
Article number	7502
Journal	Nature Communications
Volume	6
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms8502
Publication status	Published - 18 Aug 2015
Externally published	Yes

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Hayes, M. G., Urbanek, M., Ehrmann, D. A., Armstrong, L. L., Lee, J. Y., Sisk, R., Karaderi, T., Barber, T. M., McCarthy, M. I., Franks, S., Lindgren, C. M., Welt, C. K., Diamanti-Kandarakis, E., Panidis, D., Goodarzi, M. O., Azziz, R., Zhang, Y., James, R. G., Olivier, M., ... Snyder, P. (2015). Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nature Communications, 6, [7502]. https://doi.org/10.1038/ncomms8502

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 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

@article{821512b1e20548c981456de7982b70a1,

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

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.",

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

year = "2015",

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day = "18",

doi = "10.1038/ncomms8502",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations

AU - Hayes, M. Geoffrey

AU - Urbanek, Margrit

AU - Ehrmann, David A.

AU - Armstrong, Loren L.

AU - Lee, Ji Young

AU - Sisk, Ryan

AU - Karaderi, Tugce

AU - Barber, Thomas M.

AU - McCarthy, Mark I.

AU - Franks, Stephen

AU - Lindgren, Cecilia M.

AU - Welt, Corrine K.

AU - Diamanti-Kandarakis, Evanthia

AU - Panidis, Dimitrios

AU - Goodarzi, Mark O.

AU - Azziz, Ricardo

AU - Zhang, Yi

AU - James, Roland G.

AU - Olivier, Michael

AU - Kissebah, Ahmed H.

AU - Stener-Victorin, Elisabet

AU - Legro, Richard S.

AU - Dunaif, Andrea

AU - Alvero, Ruben

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

AU - Diamond, Michael P.

AU - Eisenberg, Esther

AU - Gosman, Gabriella G.

AU - Giudice, Linda C.

AU - Haisenleder, Daniel J.

AU - Huang, Hao

AU - Krawetz, Stephen A.

AU - Lucidi, Scott

AU - McGovern, Peter G.

AU - Myers, Evan R.

AU - Nestler, John E.

AU - Ohl, Dana

AU - Santoro, Nanette

AU - Schlaff, William D.

AU - Snyder, Peter

PY - 2015/8/18

Y1 - 2015/8/18

N2 - 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.

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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U2 - 10.1038/ncomms8502

DO - 10.1038/ncomms8502

M3 - Journal article

C2 - 26284813

AN - SCOPUS:84939644572

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7502

ER -

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

Abstract

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