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Associations between incident ischemic stroke events and stroke and cardiovascular disease-related genome-wide association studies single nucleotide polymorphisms in the Population Architecture Using Genomics and Epidemiology study.

TitleAssociations between incident ischemic stroke events and stroke and cardiovascular disease-related genome-wide association studies single nucleotide polymorphisms in the Population Architecture Using Genomics and Epidemiology study.
Publication TypeJournal Article
Year of Publication2012
AuthorsCarty CL, Bůžková P, Fornage M, Franceschini N, Cole S, Heiss G, Hindorff LA, Howard BV, Mann S, Martin LW, Zhang Y, Matise TC, Prentice R, Reiner AP
Secondary AuthorsKooperberg C
JournalCirc Cardiovasc Genet
Volume5
Issue2
Pagination210-6
Date Published2012 Apr 01
ISSN1942-3268
KeywordsAged, Aged, 80 and over, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, European Continental Ancestry Group, Female, Genetics, Population, Genome-Wide Association Study, Genomics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Stroke, Triglycerides
Abstract

BACKGROUND: Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored.

METHODS AND RESULTS: Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS.

CONCLUSIONS: Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.

DOI10.1161/CIRCGENETICS.111.962191
Alternate JournalCirc Cardiovasc Genet
PubMed ID22403240
PubMed Central IDPMC3402178
Grant ListN01WH42124 / WH / WHI NIH HHS / United States
M01-RR00425 / RR / NCRR NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
N01WH32102 / WH / WHI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
U01 HL041642 / HL / NHLBI NIH HHS / United States
N01WH42112 / WH / WHI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
U01CA98758 / CA / NCI NIH HHS / United States
N01WH42119 / WH / WHI NIH HHS / United States
U01 HL65520 / HL / NHLBI NIH HHS / United States
N01-HV-48195 / HV / NHLBI NIH HHS / United States
N01WH32112 / WH / WHI NIH HHS / United States
N01WH32101 / WH / WHI NIH HHS / United States
U01 HL041654 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
U01 HL65521 / HL / NHLBI NIH HHS / United States
P30 CA015704 / CA / NCI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
N01WH32119 / WH / WHI NIH HHS / United States
N01WH32105 / WH / WHI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01WH42132 / WH / WHI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01WH42121 / WH / WHI NIH HHS / United States
U01 HL41642 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
N01WH42113 / WH / WHI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01WH42125 / WH / WHI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01CA136792 / CA / NCI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
N01WH32106 / WH / WHI NIH HHS / United States
N01WH42129 / WH / WHI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01WH42108 / WH / WHI NIH HHS / United States
N01WH42118 / WH / WHI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01 HL041652 / HL / NHLBI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
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N01-HC-48050 / HC / NHLBI NIH HHS / United States
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N01-HC-85082 / HC / NHLBI NIH HHS / United States
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P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
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N01-HC-45134 / HC / NHLBI NIH HHS / United States
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U01 HL41652 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
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U01 HG004803 / HG / NHGRI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
N01WH42107 / WH / WHI NIH HHS / United States
N01WH32111 / WH / WHI NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
N01WH42130 / WH / WHI NIH HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
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N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01WH42115 / WH / WHI NIH HHS / United States
U01 HG004790-01 / HG / NHGRI NIH HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
N01WH42111 / WH / WHI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
R37CA54281 / CA / NCI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01WH32109 / WH / WHI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01WH32108 / WH / WHI NIH HHS / United States
U01 HL065521 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
N01WH42122 / WH / WHI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
N01WH32100 / WH / WHI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01WH42123 / WH / WHI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
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P01CA33619 / CA / NCI NIH HHS / United States
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U01 HG004801 / HG / NHGRI NIH HHS / United States
N01WH42110 / WH / WHI NIH HHS / United States
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N01WH42116 / WH / WHI NIH HHS / United States