4.6 Article

Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study

期刊

PLOS GENETICS
卷 7, 期 6, 页码 -

出版社

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002138

关键词

-

资金

  1. National Human Genome Research Institute (NHGRI) [U01HG004803, U01HG004798, U01HG004802, U01HG004790, U01HG004801]
  2. Johns Hopkins University from NHLBI [N01 -HV-48195]
  3. Centers for Disease Control and Prevention
  4. National Cancer Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]
  5. National Heart, Lung, and Blood Institute (NHLBI) (NIH)
  6. U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]
  7. NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-85079, N01-HC-85086]
  8. National Center for Research Resources [M01-RR00425]
  9. National Institute of Diabetes and Digestive and Kidney Disease [DK063491]
  10. National Institutes of Mental Health
  11. National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01HL080295, R01 HL087652, U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521]

向作者/读者索取更多资源

For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS-identified variants in diverse population-based studies. We genotyped 49 GWAS-identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (similar to 20,000), African American (similar to 9,000), American Indian (similar to 6,000), Mexican American/Hispanic (similar to 2,500), Japanese/East Asian (similar to 690), and Pacific Islander/Native Hawaiian (similar to 175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDLC and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据