| Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction. | |
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MedLine Citation:
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PMID: 21775993 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes, myocardial infarction, aneurysm, vertical cup disc ratio and at least five cancers. 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. |
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Authors:
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Jessica Shea; Vineeta Agarwala; Anthony A Philippakis; Jared Maguire; Eric Banks; Mark Depristo; Brian Thomson; Candace Guiducci; Robert C Onofrio; Sekar Kathiresan; Stacey Gabriel; Noël P Burtt; Mark J Daly; Leif Groop; David Altshuler; |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-07-24 |
Journal Detail:
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Title: Nature genetics Volume: 43 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-27 Completed Date: 2011-10-03 Revised Date: 2011-11-25 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 801-5 Citation Subset: IM |
Affiliation:
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Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Chromosome Mapping* Chromosomes, Human, Pair 9 / genetics* Diabetes Mellitus, Type 2 / genetics* Genetic Variation / genetics* Genome, Human Genome-Wide Association Study* Haplotypes / genetics Humans Myocardial Infarction / genetics* Polymorphism, Single Nucleotide / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL087676/HL/NHLBI NIH HHS |
| Comments/Corrections | |
Comment In:
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Circ Cardiovasc Genet. 2011 Oct;4(5):577-8
[PMID:
22010166
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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