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- Title
Extremely low-coverage sequencing and imputation increases power for genome-wide association studies.
- Authors
Pasaniuc, Bogdan; Rohland, Nadin; McLaren, Paul J; Garimella, Kiran; Zaitlen, Noah; Li, Heng; Gupta, Namrata; Neale, Benjamin M; Daly, Mark J; Sklar, Pamela; Sullivan, Patrick F; Bergen, Sarah; Moran, Jennifer L; Hultman, Christina M; Lichtenstein, Paul; Magnusson, Patrik; Purcell, Shaun M; Haas, David W; Liang, Liming; Sunyaev, Shamil
- 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 r2 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.
- Subjects
NUCLEOTIDE sequence; HUMAN genetic variation; GENE expression; TRANSCRIPTION factors; MOLECULAR genetics; GENETIC polymorphisms
- Publication
Nature Genetics, 2012, Vol 44, Issue 6, p631
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2283