期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 98, 期 12, 页码 E2006-E2012出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2013-2495
关键词
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资金
- Ferring
- Genovum
- Merck-Serono
- Organon
- Schering Plough
- Serono
Context: Genome-wide association studies (GWAS) have revealed new susceptibility loci for Chinese patients with polycystic ovary syndrome (PCOS). Because ethnic background adds to phenotypic diversities in PCOS, it seems plausible that genetic variants associated with PCOS act differently in various ethnic populations. Objective: We studied cross-ethnic effects of Chinese PCOS loci (ie, LHCGR, THADA, DENND1A, FSHR, c9orf3, YAP1, RAB5B/SUOX, HMGA2, TOX3, INSR, SUMO1P1) in patients of Northern European descent. Design: This study was a genetic association study conducted at an University Medical Center. Patients: Association was studied in 703 Dutch PCOS patients and 2164 Dutch controls. To assess the cross-ethnic effect, we performed a meta-analysis of the Dutch data combined with results of previously published studies in PCOS patients from China (n = 2254) and the United States (n = 2618). Adjusted for multiple testing, a P value <3.1 x 10(-3) was considered statistically significant. Results: Meta-analysis of the Chinese, US, and Dutch data resulted in 12 significant variants mapping to the YAP1 (P value = 1.0x 10(-9)), RAB5B/SUOX (P value = 3.8 x 10(-11)), LHCGR (P value = 4.1 x 10(-4)), THADA (P value = 2.2 x 10(-4) and P value = 1.3 x 10(-3)), DENND1A (P value = 2.3 x 10(-3) and P value = 2.5 x 10(-3)), FSHR (P value = 3.8 x 10(-5) and P value = 3.6 x 10(-4)), c9orf3 (P value = 2.0 x 10(-6) and Pvalue = 9.2 x 10(-6)), SUMO1P1 (Pvalue = 2.3 x 10(-3)) loci with odds ratios ranging from 1.19 to 1.45 and 0.79 to 0.87. Conclusions: Overall, we observed for 12 of 17 genetic variants mapping to the Chinese PCOS loci similar effect size and identical direction in PCOS patients from Northern European ancestry, indicating a common genetic risk profile for PCOS across populations. Therefore, it is expected that large GWAS in PCOS patients from Northern European ancestry will partly identify similar loci as the GWAS in Chinese PCOS patients.
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