title: Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations.
abstract: 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.
  
  
  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 4.84×10(-4) to 4.62×10(-18)), whereas LPL, TRIB1, ABCA1, APOA1-C3-A4-A5, CETP, and APOE displayed significant strongest associations for incident hyperlipidemia (P range from 1.20×10(-3) to 4.67×10(-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.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.forename: Jianfeng
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authors.lastname: Huang
authors.forename: Zengnan
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authors.lastname: Mo
authors.forename: Jiang
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authors.lastname: Wang
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authors.lastname: Chen
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authors.forename: C Charles
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authors.forename: Jichun
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authors.lastname: Chen
authors.forename: Ying
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authors.lastname: Li
authors.forename: Liancheng
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authors.lastname: Zhao
authors.forename: Hongfan
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authors.lastname: Li
authors.forename: Yongchen
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authors.forename: Jianxin
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authors.lastname: Li
authors.forename: James E
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authors.lastname: Hixson
authors.forename: Yunzhi
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authors.lastname: Li
authors.forename: Min
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authors.lastname: Cheng
authors.forename: Xiaoli
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authors.lastname: Liu
authors.forename: Jie
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authors.lastname: Cao
authors.forename: Fangcao
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authors.lastname: Liu
authors.forename: Chen
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authors.lastname: Huang
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Jinjin
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authors.lastname: Shen
authors.forename: Ling
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authors.lastname: Yu
authors.forename: Lihua
authors.initials: L
authors.lastname: Xu
authors.forename: Jianjun
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authors.lastname: Mu
authors.forename: Xianping
authors.initials: X
authors.lastname: Wu
authors.forename: Xu
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authors.lastname: Ji
authors.forename: Dongshuang
authors.initials: D
authors.lastname: Guo
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Zili
authors.initials: Z
authors.lastname: Yang
authors.forename: Renping
authors.initials: R
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Weili
authors.initials: W
authors.lastname: Yan
authors.forename: Xiaozhong
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authors.lastname: Peng
authors.forename: Dongfeng
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mesh_terms: D000328:Adult; D044466:Asian People; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008055:Lipids / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D008055:Lipids
keywords: genetic loci; genome-wide association study; hyperlipidemia; incidence; lipids