Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS)

Michelle R. Jones, Angela K. Chua, Emebet A. Mengesha, Kent D. Taylor, Yii Der I. Chen, Xiaohui Li, Ronald M. Krauss, Jerome I. Rotter, Richard Legro, Ricardo Azziz, Mark O. Goodarzi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P = 3.8 × 10 -6). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.

Original languageEnglish (US)
Pages (from-to)317-322
Number of pages6
JournalSteroids
Volume77
Issue number4
DOIs
StatePublished - Mar 10 2012

Fingerprint

Polycystic Ovary Syndrome
Medical problems
Polymorphism
Nucleotides
Genes
Insulin
Lipids
Testing
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Obesity
Genome-Wide Association Study
Hyperinsulinism
Insulin Resistance
Case-Control Studies

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Jones, M. R., Chua, A. K., Mengesha, E. A., Taylor, K. D., Chen, Y. D. I., Li, X., ... Goodarzi, M. O. (2012). Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS). Steroids, 77(4), 317-322. https://doi.org/10.1016/j.steroids.2011.12.005
Jones, Michelle R. ; Chua, Angela K. ; Mengesha, Emebet A. ; Taylor, Kent D. ; Chen, Yii Der I. ; Li, Xiaohui ; Krauss, Ronald M. ; Rotter, Jerome I. ; Legro, Richard ; Azziz, Ricardo ; Goodarzi, Mark O. / Metabolic and cardiovascular genes in polycystic ovary syndrome : A candidate-wide association study (CWAS). In: Steroids. 2012 ; Vol. 77, No. 4. pp. 317-322.
@article{9b1c1227c2954ace8b43b5855db9f5f0,
title = "Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS)",
abstract = "The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P = 3.8 × 10 -6). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.",
author = "Jones, {Michelle R.} and Chua, {Angela K.} and Mengesha, {Emebet A.} and Taylor, {Kent D.} and Chen, {Yii Der I.} and Xiaohui Li and Krauss, {Ronald M.} and Rotter, {Jerome I.} and Richard Legro and Ricardo Azziz and Goodarzi, {Mark O.}",
year = "2012",
month = "3",
day = "10",
doi = "10.1016/j.steroids.2011.12.005",
language = "English (US)",
volume = "77",
pages = "317--322",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "4",

}

Jones, MR, Chua, AK, Mengesha, EA, Taylor, KD, Chen, YDI, Li, X, Krauss, RM, Rotter, JI, Legro, R, Azziz, R & Goodarzi, MO 2012, 'Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS)', Steroids, vol. 77, no. 4, pp. 317-322. https://doi.org/10.1016/j.steroids.2011.12.005

Metabolic and cardiovascular genes in polycystic ovary syndrome : A candidate-wide association study (CWAS). / Jones, Michelle R.; Chua, Angela K.; Mengesha, Emebet A.; Taylor, Kent D.; Chen, Yii Der I.; Li, Xiaohui; Krauss, Ronald M.; Rotter, Jerome I.; Legro, Richard; Azziz, Ricardo; Goodarzi, Mark O.

In: Steroids, Vol. 77, No. 4, 10.03.2012, p. 317-322.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolic and cardiovascular genes in polycystic ovary syndrome

T2 - A candidate-wide association study (CWAS)

AU - Jones, Michelle R.

AU - Chua, Angela K.

AU - Mengesha, Emebet A.

AU - Taylor, Kent D.

AU - Chen, Yii Der I.

AU - Li, Xiaohui

AU - Krauss, Ronald M.

AU - Rotter, Jerome I.

AU - Legro, Richard

AU - Azziz, Ricardo

AU - Goodarzi, Mark O.

PY - 2012/3/10

Y1 - 2012/3/10

N2 - The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P = 3.8 × 10 -6). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.

AB - The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P = 3.8 × 10 -6). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.

UR - http://www.scopus.com/inward/record.url?scp=84857061970&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857061970&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2011.12.005

DO - 10.1016/j.steroids.2011.12.005

M3 - Article

C2 - 22178785

AN - SCOPUS:84857061970

VL - 77

SP - 317

EP - 322

JO - Steroids

JF - Steroids

SN - 0039-128X

IS - 4

ER -