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Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals.
J Clin Endocrinol Metab 2015; 100(1):E182-6JC

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

Eight hundred forty-five European subjects with PCOS and 845 controls 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 in DENND1A (P = .0002), THADA (P = .035), FSHR (P = .007), and INSR (P = .046) were associated with PCOS in Europeans. The genetic risk score, generated for each subject based on the total 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.

Authors+Show Affiliations

Department of Obstetrics and Gynecology (M.A.B.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095; Division of Endocrinology, Diabetes, and Metabolism (M.R.J., M.O.G.), Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048; Institute for Translational Genomics and Population Sciences and Department of Pediatrics (J.I.R.), Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Medical Center, Torrance, California 90502; Children's Hospital of Oakland Research Institute (R.M.K.), Oakland, California 94609; Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033; and Departments of Obstetrics and Gynecology and Medicine (R.A.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25303487

Citation

Brower, Meredith A., et al. "Further Investigation in Europeans of Susceptibility Variants for Polycystic Ovary Syndrome Discovered in Genome-wide Association Studies of Chinese Individuals." The Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 1, 2015, pp. E182-6.
Brower MA, Jones MR, Rotter JI, et al. Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals. J Clin Endocrinol Metab. 2015;100(1):E182-6.
Brower, M. A., Jones, M. R., Rotter, J. I., Krauss, R. M., Legro, R. S., Azziz, R., & Goodarzi, M. O. (2015). Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals. The Journal of Clinical Endocrinology and Metabolism, 100(1), pp. E182-6. doi:10.1210/jc.2014-2689.
Brower MA, et al. Further Investigation in Europeans of Susceptibility Variants for Polycystic Ovary Syndrome Discovered in Genome-wide Association Studies of Chinese Individuals. J Clin Endocrinol Metab. 2015;100(1):E182-6. PubMed PMID: 25303487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide 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 - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/7/15/medline SP - E182 EP - 6 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 100 IS - 1 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: Eight hundred forty-five European subjects with PCOS and 845 controls 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 in DENND1A (P = .0002), THADA (P = .035), FSHR (P = .007), and INSR (P = .046) were associated with PCOS in Europeans. The genetic risk score, generated for each subject based on the total 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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/25303487/Further_investigation_in_europeans_of_susceptibility_variants_for_polycystic_ovary_syndrome_discovered_in_genome_wide_association_studies_of_Chinese_individuals_ DB - PRIME DP - Unbound Medicine ER -