Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genomewide association studies of chinese individuals

Meredith A. Brower, Michelle R. Jones, Jerome I. Rotter, Ronald M. Krauss, Richard S. Legro, Ricardo Azziz, Mark O. Goodarzi

Research output: Contribution to journalArticle

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Abstract

Context: Two genome-wide association studies (GWAS) of polycystic ovary syndrome (PCOS) have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities. Objective: The objective of the study was to determine the effects of the Chinese GWAS loci in European-origin individuals. Design: This was a genetic association study. Setting: The study was conducted at a tertiary care academic center. Patients: Eighthundredforty-fiveEuropeansubjects withPCOSand845controls participated in the study. Interventions: Interventions included blood sampling and genotyping. Main Outcome Measure: The association between PCOS and 12 independent single-nucleotide polymorphisms mapping to seven of the Chinese GWAS loci in a European cohort was measured. Results: Variants inDENND1A(P=.0002),THADA(P=.035), FSHR (P=.007), and INSR (P=.046) were associatedwithPCOSinEuropeans.Thegeneticrisk score,generatedforeachsubjectbasedonthetotal number of risk alleles, was associated with the diagnosis of PCOS (P<.0001) and remained associated (P = .02), even after exclusion of the four variants individually associated with PCOS. Conclusions: At least four of the PCOS susceptibility loci identified in the Chinese GWAS are associated with PCOS in Europeans. The overall genetic burden for PCOS, as demonstrated by the risk score, is also associated with the diagnosis of PCOS in Europeans. The PCOS susceptibility loci identified in the Chinese GWAS are thus likely to play an important role in the etiology of PCOS across ethnicities.

Original languageEnglish (US)
Pages (from-to)E182-E186
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Polycystic Ovary Syndrome
Genes
Genome-Wide Association Study
Nucleotide Mapping
Polymorphism
Blood
Nucleotides
Genetic Association Studies
Sampling
Tertiary Care Centers
Single Nucleotide Polymorphism
Alleles
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Medicine(all)
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genomewide association studies of chinese individuals. / Brower, Meredith A.; Jones, Michelle R.; Rotter, Jerome I.; Krauss, Ronald M.; Legro, Richard S.; Azziz, Ricardo; Goodarzi, Mark O.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 1, 01.01.2015, p. E182-E186.

Research output: Contribution to journalArticle

Brower, Meredith A. ; Jones, Michelle R. ; Rotter, Jerome I. ; Krauss, Ronald M. ; Legro, Richard S. ; Azziz, Ricardo ; Goodarzi, Mark O. / Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genomewide association studies of chinese individuals. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 1. pp. E182-E186.
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abstract = "Context: Two genome-wide association studies (GWAS) of polycystic ovary syndrome (PCOS) have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities. Objective: The objective of the study was to determine the effects of the Chinese GWAS loci in European-origin individuals. Design: This was a genetic association study. Setting: The study was conducted at a tertiary care academic center. Patients: Eighthundredforty-fiveEuropeansubjects withPCOSand845controls participated in the study. Interventions: Interventions included blood sampling and genotyping. Main Outcome Measure: The association between PCOS and 12 independent single-nucleotide polymorphisms mapping to seven of the Chinese GWAS loci in a European cohort was measured. Results: Variants inDENND1A(P=.0002),THADA(P=.035), FSHR (P=.007), and INSR (P=.046) were associatedwithPCOSinEuropeans.Thegeneticrisk score,generatedforeachsubjectbasedonthetotal number of risk alleles, was associated with the diagnosis of PCOS (P<.0001) and remained associated (P = .02), even after exclusion of the four variants individually associated with PCOS. Conclusions: At least four of the PCOS susceptibility loci identified in the Chinese GWAS are associated with PCOS in Europeans. The overall genetic burden for PCOS, as demonstrated by the risk score, is also associated with the diagnosis of PCOS in Europeans. The PCOS susceptibility loci identified in the Chinese GWAS are thus likely to play an important role in the etiology of PCOS across ethnicities.",
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T1 - Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genomewide association studies of chinese individuals

AU - Brower, Meredith A.

AU - Jones, Michelle R.

AU - Rotter, Jerome I.

AU - Krauss, Ronald M.

AU - Legro, Richard S.

AU - Azziz, Ricardo

AU - Goodarzi, Mark O.

PY - 2015/1/1

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N2 - Context: Two genome-wide association studies (GWAS) of polycystic ovary syndrome (PCOS) have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities. Objective: The objective of the study was to determine the effects of the Chinese GWAS loci in European-origin individuals. Design: This was a genetic association study. Setting: The study was conducted at a tertiary care academic center. Patients: Eighthundredforty-fiveEuropeansubjects withPCOSand845controls participated in the study. Interventions: Interventions included blood sampling and genotyping. Main Outcome Measure: The association between PCOS and 12 independent single-nucleotide polymorphisms mapping to seven of the Chinese GWAS loci in a European cohort was measured. Results: Variants inDENND1A(P=.0002),THADA(P=.035), FSHR (P=.007), and INSR (P=.046) were associatedwithPCOSinEuropeans.Thegeneticrisk score,generatedforeachsubjectbasedonthetotal number of risk alleles, was associated with the diagnosis of PCOS (P<.0001) and remained associated (P = .02), even after exclusion of the four variants individually associated with PCOS. Conclusions: At least four of the PCOS susceptibility loci identified in the Chinese GWAS are associated with PCOS in Europeans. The overall genetic burden for PCOS, as demonstrated by the risk score, is also associated with the diagnosis of PCOS in Europeans. The PCOS susceptibility loci identified in the Chinese GWAS are thus likely to play an important role in the etiology of PCOS across ethnicities.

AB - Context: Two genome-wide association studies (GWAS) of polycystic ovary syndrome (PCOS) have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities. Objective: The objective of the study was to determine the effects of the Chinese GWAS loci in European-origin individuals. Design: This was a genetic association study. Setting: The study was conducted at a tertiary care academic center. Patients: Eighthundredforty-fiveEuropeansubjects withPCOSand845controls participated in the study. Interventions: Interventions included blood sampling and genotyping. Main Outcome Measure: The association between PCOS and 12 independent single-nucleotide polymorphisms mapping to seven of the Chinese GWAS loci in a European cohort was measured. Results: Variants inDENND1A(P=.0002),THADA(P=.035), FSHR (P=.007), and INSR (P=.046) were associatedwithPCOSinEuropeans.Thegeneticrisk score,generatedforeachsubjectbasedonthetotal number of risk alleles, was associated with the diagnosis of PCOS (P<.0001) and remained associated (P = .02), even after exclusion of the four variants individually associated with PCOS. Conclusions: At least four of the PCOS susceptibility loci identified in the Chinese GWAS are associated with PCOS in Europeans. The overall genetic burden for PCOS, as demonstrated by the risk score, is also associated with the diagnosis of PCOS in Europeans. The PCOS susceptibility loci identified in the Chinese GWAS are thus likely to play an important role in the etiology of PCOS across ethnicities.

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