Common variants at 6p21.1 are associated with large artery atherosclerotic stroke
- 2 September 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 44 (10), 1147-1151
- https://doi.org/10.1038/ng.2397
Abstract
Elizabeth Holliday and colleagues report a genome-wide association study for ischemic stroke. They identify common variants at 6p21.1 associated with large artery atherosclerosis (LAA), a major subtype of ischemic stroke. Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10−8) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10−4; discovery and replication combined OR = 1.21, P = 4.7 × 10−8). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.Keywords
This publication has 35 references indexed in Scilit:
- Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic strokeNature Genetics, 2012
- Estimating Missing Heritability for Disease from Genome-wide Association StudiesAmerican Journal of Human Genetics, 2011
- GCTA: A Tool for Genome-wide Complex Trait AnalysisAmerican Journal of Human Genetics, 2011
- Genome-wide association study identifies a locus at 7p15.2 associated with endometriosisNature Genetics, 2010
- MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypesGenetic Epidemiology, 2010
- Common SNPs explain a large proportion of the heritability for human heightNature Genetics, 2010
- Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic reviewThe Lancet Neurology, 2009
- Genetic Control of Human Brain Transcript Expression in Alzheimer DiseaseAmerican Journal of Human Genetics, 2009
- Histone modifications at human enhancers reflect global cell-type-specific gene expressionNature, 2009
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004