Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction
(2011) In Nature Genetics 43(8). p.114-801- Abstract
- Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes(1-4), myocardial infarction(5-7), aneurysm(8), vertical cup disc ratio(9) and at least five cancers(10-16). 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... (More)
- Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes(1-4), myocardial infarction(5-7), aneurysm(8), vertical cup disc ratio(9) and at least five cancers(10-16). 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. (Less)
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https://lup.lub.lu.se/record/2071980
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Genetics
- volume
- 43
- issue
- 8
- pages
- 114 - 801
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000293178300018
- scopus:79960930495
- ISSN
- 1546-1718
- DOI
- 10.1038/ng.871
- language
- English
- LU publication?
- yes
- id
- 6bad232f-f2d9-4973-862b-832617506639 (old id 2071980)
- date added to LUP
- 2016-04-01 13:40:22
- date last changed
- 2024-04-10 08:40:06
@article{6bad232f-f2d9-4973-862b-832617506639,
abstract = {{Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes(1-4), myocardial infarction(5-7), aneurysm(8), vertical cup disc ratio(9) and at least five cancers(10-16). 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.}},
author = {{Shea, Jessica and Agarwala, Vineeta and Philippakis, Anthony A. and Maguire, Jared and Banks, Eric and DePristo, Mark and Thomson, Brian and Guiducci, Candace and Onofrio, Robert C. and Kathiresan, Sekar and Gabriel, Stacey and Burtt, Noel P. and Daly, Mark J. and Groop, Leif and Altshuler, David}},
issn = {{1546-1718}},
language = {{eng}},
number = {{8}},
pages = {{114--801}},
publisher = {{Nature Publishing Group}},
series = {{Nature Genetics}},
title = {{Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction}},
url = {{http://dx.doi.org/10.1038/ng.871}},
doi = {{10.1038/ng.871}},
volume = {{43}},
year = {{2011}},
}