Imputation of structural variants using a multi-ancestry long-read sequencing panel enables identification of disease associations
Using Oxford Nanopore sequencing, Noyvert et al. captured SVs in 888 samples from the 1000 Genomes Project, creating a reference panel that was then used for the first large-scale genome-wide SV-association study. The authors identified thousands of disease-related DNA alterations, and SV analysis highlighted potential causal genes for respiratory diseases that were missed in previous studies.
Key points:
Previous genome-wide association studies (GWAS) focused on SNVs because SVs are often longer than the maximum read length of short-read sequencing methods.
By nanopore sequencing 888 samples from mixed ancestry backgrounds, the authors created an SV panel that was used to impute SVs in nearly 500,000 UK Biobank participants.
The authors identified 3,858 SV associations across 32 disease-relevant traits, of which 1,258 were novel.
SV analysis highlighted CFDP1, MEGF6, AAGAB, and FLI1 as potential causal genes for respiratory diseases that were missed by previous GWAS.
Studying SVs could improve genetic risk prediction and identification of potential drug targets in the future.
Sample type: human DNA from the 1000 genomes project