title: Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.
abstract: 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 (~20,000), African American (~9,000), American Indian (~6,000), Mexican American/Hispanic (~2,500), Japanese/East Asian (~690), and Pacific Islander/Native Hawaiian (~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 HDL-C 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.
authors: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America.
authors: Logan
authors: L
authors: Dumitrescu
authors: Cara L
authors: CL
authors: Carty
authors: Kira
authors: K
authors: Taylor
authors: Fredrick R
authors: FR
authors: Schumacher
authors: Lucia A
authors: LA
authors: Hindorff
authors: José L
authors: JL
authors: Ambite
authors: Garnet
authors: G
authors: Anderson
authors: Lyle G
authors: LG
authors: Best
authors: Kristin
authors: K
authors: Brown-Gentry
authors: Petra
authors: P
authors: Bůžková
authors: Christopher S
authors: CS
authors: Carlson
authors: Barbara
authors: B
authors: Cochran
authors: Shelley A
authors: SA
authors: Cole
authors: Richard B
authors: RB
authors: Devereux
authors: Dave
authors: D
authors: Duggan
authors: Charles B
authors: CB
authors: Eaton
authors: Myriam
authors: M
authors: Fornage
authors: Nora
authors: N
authors: Franceschini
authors: Jeff
authors: J
authors: Haessler
authors: Barbara V
authors: BV
authors: Howard
authors: Karen C
authors: KC
authors: Johnson
authors: Sandra
authors: S
authors: Laston
authors: Laurence N
authors: LN
authors: Kolonel
authors: Elisa T
authors: ET
authors: Lee
authors: Jean W
authors: JW
authors: MacCluer
authors: Teri A
authors: TA
authors: Manolio
authors: Sarah A
authors: SA
authors: Pendergrass
authors: Miguel
authors: M
authors: Quibrera
authors: Ralph V
authors: RV
authors: Shohet
authors: Lynne R
authors: LR
authors: Wilkens
authors: Christopher A
authors: CA
authors: Haiman
authors: Loïc
authors: L
authors: Le Marchand
authors: Steven
authors: S
authors: Buyske
authors: Charles
authors: C
authors: Kooperberg
authors: Kari E
authors: KE
authors: North
authors: Dana C
authors: DC
authors: Crawford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics; D008077:Lipoproteins, LDL / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D014280:Triglycerides / Q000235:genetics; D055815:Young Adult
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides