Format

Send to

Choose Destination
Nat Genet. 2012 May 20;44(6):631-5. doi: 10.1038/ng.2283.

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

Author information

1
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. bpasaniu@hsph.harvard.edu

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.

PMID:
22610117
PMCID:
PMC3400344
DOI:
10.1038/ng.2283
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Grant support

Publication types

MeSH terms

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center