Functional genomics of PCOS: From GWAS to molecular mechanisms

Jan M. McAllister; Richard S. Legro; Bhavi P. Modi; Jerome F. Strauss

doi:10.1016/j.tem.2014.12.004

Functional genomics of PCOS: From GWAS to molecular mechanisms

Jan M. McAllister, Richard S. Legro, Bhavi P. Modi, Jerome F. Strauss

Research output: Contribution to journal › Review article › peer-review

160 Scopus citations

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.

Original language	English (US)
Pages (from-to)	118-124
Number of pages	7
Journal	Trends in Endocrinology and Metabolism
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.tem.2014.12.004
State	Published - Mar 1 2015

All Science Journal Classification (ASJC) codes

Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.tem.2014.12.004

Cite this

@article{48f8a629ef4140acb59b12e7c064c9c1,

title = "Functional genomics of PCOS: From GWAS to molecular mechanisms",

abstract = "Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.",

author = "McAllister, {Jan M.} and Legro, {Richard S.} and Modi, {Bhavi P.} and Strauss, {Jerome F.}",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd.",

year = "2015",

month = mar,

day = "1",

doi = "10.1016/j.tem.2014.12.004",

language = "English (US)",

volume = "26",

pages = "118--124",

journal = "Trends in Endocrinology and Metabolism",

issn = "1043-2760",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Functional genomics of PCOS

T2 - From GWAS to molecular mechanisms

AU - McAllister, Jan M.

AU - Legro, Richard S.

AU - Modi, Bhavi P.

AU - Strauss, Jerome F.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.

AB - Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.

UR - http://www.scopus.com/inward/record.url?scp=84923580418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923580418&partnerID=8YFLogxK

U2 - 10.1016/j.tem.2014.12.004

DO - 10.1016/j.tem.2014.12.004

M3 - Review article

C2 - 25600292

AN - SCOPUS:84923580418

SN - 1043-2760

VL - 26

SP - 118

EP - 124

JO - Trends in Endocrinology and Metabolism

JF - Trends in Endocrinology and Metabolism

IS - 3

ER -

Functional genomics of PCOS: From GWAS to molecular mechanisms

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this