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Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos.

TitleGenetic architecture of lipid traits in the Hispanic community health study/study of Latinos.
Publication TypePublication
Year2017
AuthorsGraff M, Emery LS, Justice AE, Parra E, Below JE, Palmer ND, Gao C, Duan Q, Valladares-Salgado A, Cruz M, Morrison AC, Boerwinkle E, Whitsel EA, Kooperberg C, Reiner A, Li Y, Rodriguez CJose, Talavera GA, Langefeld CD, Wagenknecht LE, Norris JM, Taylor KD, Papanicolaou G, Kenny E, Loos RJF, Chen Y-DIda, Laurie C, Sofer T, North KE
JournalLipids Health Dis
Volume16
Issue1
Pagination200
Date Published2017 Oct 12
ISSN1476-511X
KeywordsAdolescent, Adult, Aged, Alleles, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Female, Gene Frequency, Genetic Loci, Genome, Human, genome-wide association study, Genotype, Hispanic Americans, Humans, Lipid Metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Public Health, Quantitative Trait, Heritable, triglycerides, United States
Abstract

BACKGROUND: Despite ethnic disparities in lipid profiles, there are few genome-wide association studies investigating genetic variation of lipids in non-European ancestry populations. In this study, we present findings from genetic association analyses for total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides in a large Hispanic/Latino cohort in the U.S., the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).METHODS: We estimated a heritability of approximately 20% for each lipid trait, similar to previous estimates in Europeans. To search for novel lipid loci, we performed conditional association analysis in which the statistical model was adjusted for previously reported SNPs associated with any of the four lipid traits. SNPs that remained genome-wide significant (P < 5 × 10) after conditioning on known loci were evaluated for replication.RESULTS: We identified eight potentially novel lipid signals with minor allele frequencies <1%, none of which replicated. We tested previously reported SNP-trait associations for generalization to Hispanics/Latinos via a statistical framework. The generalization analysis revealed that approximately 50% of previously established lipid variants generalize to HCHS/SOL based on directional FDR r-value < 0.05. Some failures to generalize were due to lack of power.CONCLUSIONS: These results demonstrate that many loci associated with lipid levels are shared across populations.

DOI10.1186/s12944-017-0591-6
Alternate JournalLipids Health Dis
PubMed ID29025430
PubMed Central IDPMC5639746
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
U01 DK085501 / DK / NIDDK NIH HHS / United States
U01 HG007417 / HG / NHGRI NIH HHS / United States
R01 DK085175 / DK / NIDDK NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
R01 HG006292 / HG / NHGRI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 HG007112 / HG / NHGRI NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
R00 HL130580 / HL / NHLBI NIH HHS / United States
R01 HL129132 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
R01 HL088457 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
R01 HL060944 / HL / NHLBI NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
R01 HL102830 / HL / NHLBI NIH HHS / United States
R01 DK073541 / DK / NIDDK NIH HHS / United States
U01 HL047902 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R01 HL061019 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
R01 AI085014 / AI / NIAID NIH HHS / United States
R01 HL060919 / HL / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
R01 DK079888 / DK / NIDDK NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
P60 DK020595 / DK / NIDDK NIH HHS / United States
MS#: 
0330
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published