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Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations

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机构: [1]Peking Union Med Coll, Beijing 100037, Peoples R China; [2]Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China; [3]Chinese Acad Med Sci, Inst Basic Med Sci, Natl Ctr Cardiovasc Dis, Hypertens Div,Fuwai Hosp, Beijing 100037, Peoples R China; [4]Guangxi Med Univ, Sch Publ Hlth, Med Sci Res Ctr, Ctr Genom & Personalized Med,Dept Occupat Hlth &, Nanning, Guangxi, Peoples R China; [5]Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA; [6]Natl Human Genome Ctr, Beijing, Peoples R China; [7]Capital Med Univ, Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China; [8]Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA; [9]Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol, Houston, TX USA; [10]Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China; [11]Yancheng Municipal Ctr Dis Control & Prevent, Yancheng, Jiangsu, Peoples R China; [12]Fujian Prov Peoples Hosp, Dept Cardiol, Fuzhou, Fujian, Peoples R China; [13]Beihua Univ, Affiliated Hosp, Dept Cardiol, Jilin, Jilin, Peoples R China; [14]Xi An Jiao Tong Univ, Coll Med, Affiliated Hosp 1, Dept Cardiol, Xian 710049, Shaanxi, Peoples R China; [15]Sichuan Ctr Dis Control & Prevent, Ctr Chron & Noncommunicable Dis Control & Prevent, Chengdu, Sichuan, Peoples R China; [16]Xinle Red Cross Hosp, Dept Internal Med, Xinle, Hebei, Peoples R China; [17]Yuxian Renmin Hosp, Dept Internal Med, Yuxian, Shanxi, Peoples R China; [18]Changshu Ctr Dis Control & Prevent, Changshu, Peoples R China; [19]Nantong Ctr Dis Control & Prevent, Nantong, Jiangsu, Peoples R China; [20]Shijiazhuang Greatwall Hosp, Dept Internal Med, Shijiazhuang, Hebei, Peoples R China; [21]Hanzhong Peoples Hosp, Dept Cardiol, Hanzhong, Shaanxi, Peoples R China; [22]Fudan Univ, Childrens Hosp, Dept Clin Epidemiol, Shanghai 200433, Peoples R China; [23]Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China
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关键词: genetic loci incidence lipids hyperlipidemia genome-wide association study

摘要:
Background- Multiple genetic loci associated with lipid levels have been identified predominantly in Europeans, and the issue of to what extent these genetic loci can predict blood lipid levels increases over time and the incidence of future hyperlipidemia remains largely unknown. Methods and Results- We conducted a meta-analysis of genome-wide association studies of lipid levels in 8344 subjects followed by replication studies including 14 739 additional individuals. We replicated 17 previously reported loci. We also newly identified 3 Chinese-specific variants in previous regions (HLA-C, LIPG, and LDLR) with genome-wide significance. Almost all the variants contributed to lipid levels change and incident hyperlipidemia > 8.1-year follow-up among 6428 individuals of a prospective cohort study. The strongest associations for lipid levels change were detected at LPL, TRIB1, APOA1-C3-A4-A5, LIPC, CETP, and LDLR (P range from 4.84x10(-4) to 4.62x10(-18)), whereas LPL, TRIB1, ABCA1, APOA1-C3-A4-A5, CETP, and APOE displayed significant strongest associations for incident hyperlipidemia (P range from 1.20x10(-3) to 4.67x10(-16)). The 4 lipids genetic risk scores were independently associated with linear increases in their corresponding lipid levels and risk of incident hyperlipidemia. A C-statistics analysis showed significant improvement in the prediction of incident hyperlipidemia on top of traditional risk factors including the baseline lipid levels. Conclusions- These findings identified some evidence for allelic heterogeneity in Chinese when compared with Europeans in relation to lipid associations. The individual variants and those cumulative effects were independent risk factors for lipids increase and incident hyperlipidemia.

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出版当年[2015]版:
大类 | 2 区 医学
小类 | 2 区 心脏和心血管系统 2 区 遗传学
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Q1 GENETICS & HEREDITY Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
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影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者机构: [1]Peking Union Med Coll, Beijing 100037, Peoples R China; [2]Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China;
通讯作者:
通讯机构: [1]Peking Union Med Coll, Beijing 100037, Peoples R China; [2]Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China; [23]Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China
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