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论文题目: Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
英文论文题目: Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
第一作者: Spracklen, CN; Chen, P; Kim, YJ; Wang, X; Cai, H; Li, SX; Long, JR; Wu, Y; Wang, YX; Takeuchi, F; Wu, JY; Jung, KJ; Hu, C; Akiyama, K; Zhang, YH;et al.
英文第一作者: Spracklen, CN; Chen, P; Kim, YJ; Wang, X; Cai, H; Li, SX; Long, JR; Wu, Y; Wang, YX; Takeuchi, F; Wu, JY; Jung, KJ; Hu, C; Akiyama, K; Zhang, YH;et al.
联系作者: Sim, XL (reprint author), Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
英文联系作者: Sim, XL (reprint author), Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
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发表年度: 2017
卷: 26
期: 9
页码: 1770-1784
摘要: Large-scale meta-analyses of genome-wide association studies (GWAS) have identified > 175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 x 10(-8)) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 x 10(-9)), NCOA2 (P = 1.6 x 10(-8)), and NID2-PTGDR (P = 4.2 x 10(-8)), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 x 10(-10)). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log(10)Bayes Factor a 6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 x 10(-5)) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.
英文摘要: Large-scale meta-analyses of genome-wide association studies (GWAS) have identified > 175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 x 10(-8)) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 x 10(-9)), NCOA2 (P = 1.6 x 10(-8)), and NID2-PTGDR (P = 4.2 x 10(-8)), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 x 10(-10)). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log(10)Bayes Factor a 6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 x 10(-5)) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.
刊物名称: HUMAN MOLECULAR GENETICS
英文刊物名称: HUMAN MOLECULAR GENETICS
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学科: Biochemistry & Molecular Biology; Genetics & Heredity
英文学科: Biochemistry & Molecular Biology; Genetics & Heredity
影响因子: 5.34
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论文类别: Article
英文论文类别: Article
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