Extremely low-coverage sequencing and imputation increases power for genome-wide association studies.

Nat Genet
Authors
Keywords
Abstract

Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5×) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24× average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power.

Year of Publication
2012
Journal
Nat Genet
Volume
44
Issue
6
Pages
631-5
Date Published
2012 May 20
ISSN
1546-1718
URL
DOI
10.1038/ng.2283
PubMed ID
22610117
PubMed Central ID
PMC3400344
Links
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