Improving imputation in disease-relevant regions: lessons from cystic fibrosis.

ABSTRACT: Does genotype imputation with public reference panels identify variants contributing to disease? Genotype imputation using the 1000 Genomes Project (1KG; 2504 individuals) displayed poor coverage at the causal cystic fibrosis (CF) transmembrane conductance regulator (CFTR) locus for the International CF Gene Modifier Consortium. Imputation with the larger Haplotype Reference Consortium (HRC; 32,470 individuals) displayed improved coverage but low sensitivity of variants clinically relevant for CF. A hybrid reference that combined whole genome sequencing (WGS) from 101 CF individuals with the 1KG imputed a greater number of single-nucleotide variants (SNVs) that would be analyzed in a genetic association study (r² ≥ 0.3 and MAF ≥ 0.5%) than imputation with the HRC,

SUBMITTER: Panjwani N 

PROVIDER: S-EPMC5861096 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature