Back

Imputation and polygenic score performance of low coverage whole-genome sequencing and genotyping arrays in diverse human populations

Nguyen, P. T.; Nguyen, V. T.; Nguyen, D. T.; Duong, H. H.-T.

2025-07-22 genomics
10.1101/2025.07.18.665609 bioRxiv
Show abstract

Genome-wide association studies and polygenic score analysis rely on large-scale genotypic data, traditionally obtained through SNP arrays and imputation. However, low coverage whole-genome sequencing has emerged as a promising alternative. This study presents a comprehensive comparison of imputation accuracy and polygenic score performance between eight high-performance genotyping arrays and six low coverage whole-genome sequencing coverage levels (0.5-2x) across diverse populations. We analyze data from 2,504 individuals in the 1000 Genomes Project using a 10-fold cross-imputation strategy to evaluate imputation accuracy and polygenic score performance for four complex traits. Our results demonstrate that low-pass whole-genome sequencing performs competitively with population-specific arrays in both imputation accuracy and polygenic score estimation. Interestingly, low coverage whole-genome sequencing shows superior performances compared to arrays in underrepresented populations and for rare and low-frequency variants. Our findings suggest that low coverage whole-genome sequencing offers a flexible and powerful alternative to genotyping arrays for large-scale genetic studies, particularly in diverse or underrepresented populations.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.