efficiency and power as a function of sequence coverage, snp array density, and imputation效率和功率的函数序列覆盖率,snp阵列密度,和非难.pdfVIP

Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation 1,2 1,2,3,4 1 1 1 Jason Flannick , Joshua M. Korn , Pierre Fontanillas , George B. Grant , Eric Banks , Mark A. Depristo1, David Altshuler1,2,5* 1 Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America, 2 Department of Molecular Biology and Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 3 Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, United States of America, 4 Graduate Program in Biophysics, Harvard University, Cambridge, Massachusetts, United States of America, 5 Department of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts, United States of America Abstract High coverage whole genome sequencing provides near complete information about genetic variation. However, other technologies can be more efficient in some settings by (a) reducing redundant coverage within samples and (b) exploiting patterns of genetic variation across samples. To characterize as many samples as possible, many genetic studies therefore employ lower coverage sequencing or SNP array genotyping coupled to statistical imputation. To compare these approaches individually and in conjunction, we developed a statistical framework to estimate genotypes jointly from sequence reads, array intensities, and imputation. In European samples, we find similar sensitivity (89%) and specificity (99.6%) from imputation with either 1 6sequencing or 1 M SNP arrays. Sensitivity is increased, particularly for low-frequency polymorphisms (MAF v5%), when low coverage seq