The hazards of genotype imputation when mapping disease susceptibility variants.

ABSTRACT:

Background

The cost-free increase in statistical power of using imputation to infer missing genotypes is undoubtedly appealing, but is it hazard-free? This case study of three type-2 diabetes (T2D) loci demonstrates that it is not; it sheds light on why this is so and raises concerns as to the shortcomings of imputation at disease loci, where haplotypes differ between cases and reference panel.

Results

T2D-associated variants were previously identified using targeted sequencing. We removed these significantly associated SNPs and used neighbouring SNPs to infer them by imputation. We compared imputed with observed genotypes, examined the altered pattern of T2D-SNP association, and investigated the cause of imputation errors by studying haplotype structure. Most T2D variants w

SUBMITTER: Lau W 

PROVIDER: S-EPMC10763476 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature