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论文题目: Rare variant associations with waist-to-hip ratio in European-American and African-American women from the NHLBI-Exome Sequencing Project
英文论文题目: Rare variant associations with waist-to-hip ratio in European-American and African-American women from the NHLBI-Exome Sequencing Project
第一作者: Kan, MY; Auer, PL; Wang, GT; Bucasas, KL; Hooker, S; Rodriguez, A; Li, B; Ellis, J; Cupples, LA; Chen, YDI; Dupuis, J; Fox, CS; Gross, MD; Smith, JD; Heard-Costa, N; Meigs, JB; Pankow, JS; Rotter, JI; Siscovick, D; Wilson, JG; Shendure, J; Jackson, R; Peters, U; Zhong, H; Lin, DY; Hsu, L; Franceschini, N; Carlson, C; Abecasis, G; Gabriel, S; Bamshad, MJ; Altshuler, D; Nickerson, DA; North, KE; Lange, LA; Reiner, AP; Leal, SM
英文第一作者: Kan, MY; Auer, PL; Wang, GT; Bucasas, KL; Hooker, S; Rodriguez, A; Li, B; Ellis, J; Cupples, LA; Chen, YDI; Dupuis, J; Fox, CS; Gross, MD; Smith, JD; Heard-Costa, N; Meigs, JB; Pankow, JS; Rotter, JI; Siscovick, D; Wilson, JG; Shendure, J; Jackson, R; Peters, U; Zhong, H; Lin, DY; Hsu, L; Franceschini, N; Carlson, C; Abecasis, G; Gabriel, S; Bamshad, MJ; Altshuler, D; Nickerson, DA; North, KE; Lange, LA; Reiner, AP; Leal, SM
联系作者: Leal, SM (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, One Baylor Plaza 700D, Houston, TX 77030 USA.
英文联系作者: Leal, SM (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, One Baylor Plaza 700D, Houston, TX 77030 USA.
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发表年度: 2016
卷: 24
期: 8
页码: 1181-1187
摘要: Waist-to-hip ratio (WHR), a relative comparison of waist and hip circumferences, is an easily accessible measurement of body fat distribution, in particular central abdominal fat. A high WHR indicates more intra-abdominal fat deposition and is an established risk factor for cardiovascular disease and type 2 diabetes. Recent genome-wide association studies have identified numerous common genetic loci influencing WHR, but the contributions of rare variants have not been previously reported. We investigated rare variant associations with WHR in 1510 European-American and 1186 African-American women from the National Heart, Lung, and Blood Institute-Exome Sequencing Project. Association analysis was performed on the gene level using several rare variant association methods. The strongest association was observed for rare variants in IKBKB (P = 4.0 x 10(-8)) in European-Americans, where rare variants in this gene are predicted to decrease WHRs. The activation of the IKBKB gene is involved in inflammatory processes and insulin resistance, which may affect normal food intake and body weight and shape. Meanwhile, aggregation of rare variants in COBLL1, previously found to harbor common variants associated with WHR and fasting insulin, were nominally associated (P = 2.23 x 10(-4)) with higher WHR in European-Americans. However, these significant results are not shared between African-Americans and European-Americans that may be due to differences in the allelic architecture of the two populations and the small sample sizes. Our study indicates that the combined effect of rare variants contribute to the inter-individual variation in fat distribution through the regulation of insulin response.
英文摘要: Waist-to-hip ratio (WHR), a relative comparison of waist and hip circumferences, is an easily accessible measurement of body fat distribution, in particular central abdominal fat. A high WHR indicates more intra-abdominal fat deposition and is an established risk factor for cardiovascular disease and type 2 diabetes. Recent genome-wide association studies have identified numerous common genetic loci influencing WHR, but the contributions of rare variants have not been previously reported. We investigated rare variant associations with WHR in 1510 European-American and 1186 African-American women from the National Heart, Lung, and Blood Institute-Exome Sequencing Project. Association analysis was performed on the gene level using several rare variant association methods. The strongest association was observed for rare variants in IKBKB (P = 4.0 x 10(-8)) in European-Americans, where rare variants in this gene are predicted to decrease WHRs. The activation of the IKBKB gene is involved in inflammatory processes and insulin resistance, which may affect normal food intake and body weight and shape. Meanwhile, aggregation of rare variants in COBLL1, previously found to harbor common variants associated with WHR and fasting insulin, were nominally associated (P = 2.23 x 10(-4)) with higher WHR in European-Americans. However, these significant results are not shared between African-Americans and European-Americans that may be due to differences in the allelic architecture of the two populations and the small sample sizes. Our study indicates that the combined effect of rare variants contribute to the inter-individual variation in fat distribution through the regulation of insulin response.
刊物名称: EUROPEAN JOURNAL OF HUMAN GENETICS
英文刊物名称: EUROPEAN JOURNAL OF HUMAN 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: 4.287
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论文类别: Article
英文论文类别: Article
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