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- W2023742867 abstract "David Altshuler and colleagues compare strategies to fine map the association of common variants at 9p21 with type 2 diabetes and myocardial infarction. Their study provides an empirical assessment of the performance of targeted sequencing and imputation-based approaches to comprehensively assess genetic variation in disease-associated regions. Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes1,2,3,4, myocardial infarction5,6,7, aneurysm8, vertical cup disc ratio9 and at least five cancers10,11,12,13,14,15,16. Here we compare approaches to more comprehensively assess genetic variation in the region. We carried out targeted sequencing at high coverage in 47 individuals and compared the results to pilot data from the 1000 Genomes Project. We imputed variants into type 2 diabetes and myocardial infarction cohorts directly from targeted sequencing, from a genotyped reference panel derived from sequencing and from 1000 Genomes Project low-coverage data. Polymorphisms with frequency >5% were captured well by all strategies. Imputation of intermediate-frequency polymorphisms required a higher density of tag SNPs in disease samples than is available on first-generation genome-wide association study (GWAS) arrays. Our association analyses identified more comprehensive sets of variants showing equivalent statistical association with type 2 diabetes or myocardial infarction, but did not identify stronger associations than the original GWAS signals." @default.
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- W2023742867 date "2011-07-24" @default.
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- W2023742867 title "Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction" @default.
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- W2023742867 doi "https://doi.org/10.1038/ng.871" @default.
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