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 S. Legro; Ricardo Azziz; Mark O. Goodarzi

doi:10.1016/j.steroids.2011.12.005

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 S. Legro, Ricardo Azziz, Mark O. Goodarzi

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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 language	English (US)
Pages (from-to)	317-322
Number of pages	6
Journal	Steroids
Volume	77
Issue number	4
DOIs	https://doi.org/10.1016/j.steroids.2011.12.005
State	Published - Mar 10 2012

Keywords

Candidate-wide association study
Cardio-Metabochip
Genetic association
Polycystic ovary syndrome
Single nucleotide polymorphism

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology
Pharmacology
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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10.1016/j.steroids.2011.12.005

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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.",

keywords = "Candidate-wide association study, Cardio-Metabochip, Genetic association, Polycystic ovary syndrome, Single nucleotide polymorphism",

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 Legro, {Richard S.} and Ricardo Azziz and Goodarzi, {Mark O.}",

note = "Funding Information: This study was supported by National Institutes of Health Grants U54-HD034449 to RSL, RR10732 and C06-RR016499 to Pennsylvania State University General Clinical Research Center (GCRC), R01-HD029364 to RA, R01-HL069757 to RMK, R01-DK079888 to MOG, CTSI Grant UL1RR033176, DERC Grant P30-DK063491, Grants to the Reproductive Medicine Network (U01-HD55925, U10-HD27049, U01-HD38997, U10-HD39005, U10-HD27011, U10-HD33172, U10-HD38988, U10-HD38992, U10-HD38998, U10-HD38999), and the Winnick Clinical Scholars Award to MOG. Appendix A ",

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doi = "10.1016/j.steroids.2011.12.005",

language = "English (US)",

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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 S.

AU - Azziz, Ricardo

AU - Goodarzi, Mark O.

N1 - Funding Information: This study was supported by National Institutes of Health Grants U54-HD034449 to RSL, RR10732 and C06-RR016499 to Pennsylvania State University General Clinical Research Center (GCRC), R01-HD029364 to RA, R01-HL069757 to RMK, R01-DK079888 to MOG, CTSI Grant UL1RR033176, DERC Grant P30-DK063491, Grants to the Reproductive Medicine Network (U01-HD55925, U10-HD27049, U01-HD38997, U10-HD39005, U10-HD27011, U10-HD33172, U10-HD38988, U10-HD38992, U10-HD38998, U10-HD38999), and the Winnick Clinical Scholars Award to MOG. Appendix A

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.

KW - Candidate-wide association study

KW - Cardio-Metabochip

KW - Genetic association

KW - Polycystic ovary syndrome

KW - Single nucleotide polymorphism

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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