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

被引：124

作者：

Dumitrescu, Logan ^{[1
]}

Carty, Cara L. ^{[2
]}

Taylor, Kira ^{[3
]}

Schumacher, Fredrick R. ^{[4
]}

Hindorff, Lucia A. ^{[5
]}

Ambite, Jose L. ^{[6
]}

Anderson, Garnet ^{[2
]}

Best, Lyle G. ^{[7
]}

Brown-Gentry, Kristin ^{[1
]}

Buzkova, Petra ^{[8
]}

Carlson, Christopher S. ^{[2
]}

Cochran, Barbara ^{[9
]}

Cole, Shelley A. ^{[10
]}

Devereux, Richard B. ^{[11
]}

Duggan, Dave ^{[12
]}

Eaton, Charles B. ^{[13
]}

Fornage, Myriam ^{[14
,15
]}

Franceschini, Nora ^{[3
]}

Haessler, Jeff ^{[2
]}

Howard, Barbara V. ^{[16
]}

Johnson, Karen C. ^{[17
]}

Laston, Sandra ^{[10
]}

Kolonel, Laurence N. ^{[18
]}

Lee, Elisa T. ^{[19
]}

MacCluer, Jean W. ^{[10
]}

Manolio, Teri A. ^{[5
]}

Pendergrass, Sarah A. ^{[1
]}

Quibrera, Miguel ^{[20
]}

Shohet, Ralph V. ^{[21
]}

Wilkens, Lynne R. ^{[18
]}

Haiman, Christopher A. ^{[4
]}

Le Marchand, Loic ^{[18
]}

Buyske, Steven ^{[22
]}

Kooperberg, Charles ^{[2
]}

North, Kari E. ^{[3
,23
]}

Crawford, Dana C. ^{[1
,24
]}

机构：

[1] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37203 USA

[2] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[3] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[4] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[5] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA

[6] Univ So Calif, Inst Informat Sci, Los Angeles, CA USA

[7] Missouri Breaks Ind Res, Timber Lake, SD USA

[8] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[9] Baylor Coll Med, Sponsored Programs, Houston, TX 77030 USA

[10] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA

[11] Weill Cornell Med Coll, Dept Med, New York, NY USA

[12] Translat Genom Res Inst, Phoenix, AZ USA

[13] Brown Univ, Sch Med, Alpert Med Sch, Dept Family Med & Community Hlth, Providence, RI 02912 USA

[14] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA

[15] Univ Texas Hlth Sci Ctr, Div Epidemiol, Sch Publ Hlth, Houston, TX USA

[16] Medstar Res Inst, Washington, DC USA

[17] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA

[18] Univ Hawaii, John A Burns Sch Med, Program Epidemiol, Ctr Canc,Dept Med, Honolulu, HI 96822 USA

[19] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA

[20] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA

[21] Univ Hawaii, John A Burns Sch Med, Dept Med, Cardiovasc Res Ctr, Honolulu, HI 96822 USA

[22] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA

[23] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA

[24] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

来源：

PLOS GENETICS | 2011年 / 7卷 / 06期

关键词：

DENSITY-LIPOPROTEIN-CHOLESTEROL; WIDE ASSOCIATION ANALYSIS; NUTRITION EXAMINATION SURVEY; CORONARY-ARTERY-DISEASE; AFRICAN-AMERICANS; CARDIOVASCULAR-DISEASE; BLOOD-LIPIDS; JAPANESE POPULATION; TRIGLYCERIDE LEVELS; ALCOHOL DEPENDENCE;

D O I：

10.1371/journal.pgen.1002138

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：15

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