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Using off-target data from whole-exome sequencing to improve genotyping accuracy, association analysis and polygenic risk prediction
- Source :
- Briefings in bioinformatics. 22(3)
- Publication Year :
- 2020
-
Abstract
- Whole-exome sequencing (WES) has been widely used to study the role of protein-coding variants in genetic diseases. Non-coding regions, typically covered by sparse off-target data, are often discarded by conventional WES analyses. Here, we develop a genotype calling pipeline named WEScall to analyse both target and off-target data. We leverage linkage disequilibrium shared within study samples and from an external reference panel to improve genotyping accuracy. In an application to WES of 2527 Chinese and Malays, WEScall can reduce the genotype discordance rate from 0.26% (SE= 6.4 × 10−6) to 0.08% (SE = 3.6 × 10−6) across 1.1 million single nucleotide polymorphisms (SNPs) in the deeply sequenced target regions. Furthermore, we obtain genotypes at 0.70% (SE = 3.0 × 10−6) discordance rate across 5.2 million off-target SNPs, which had ~1.2× mean sequencing depth. Using this dataset, we perform genome-wide association studies of 10 metabolic traits. Despite of our small sample size, we identify 10 loci at genome-wide significance (P
- Subjects :
- Linkage disequilibrium
Genotype
Muscle Proteins
Single-nucleotide polymorphism
Genome-wide association study
Computational biology
Biology
Polymorphism, Single Nucleotide
Deep sequencing
Linkage Disequilibrium
03 medical and health sciences
0302 clinical medicine
Anion Exchange Protein 1, Erythrocyte
Exome Sequencing
Humans
Genetic Predisposition to Disease
Molecular Biology
Genotyping
Exome sequencing
030304 developmental biology
Genetic association
0303 health sciences
High-Throughput Nucleotide Sequencing
030217 neurology & neurosurgery
Information Systems
Subjects
Details
- ISSN :
- 14774054
- Volume :
- 22
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Briefings in bioinformatics
- Accession number :
- edsair.doi.dedup.....e0b1cf672538898066f2f7cff8da665a