Study Shows Potential of Ultra-Low Coverage Whole-Genome Sequencing for GWAS

Ultra-low coverage whole genome sequencing (ulcWGS) can effectively be used for genotype imputation, highlighting its utility in genome-wide association studies (GWAS), according to a study appearing this week in Genome Medicine. Recently, low (0.5-1x) and extremely low-coverage (0.1-0.5x) WGS have emerged as affordable alternatives to conventional WGS for genotyping. However, it remains unclear whether ulcWGS — below 0.1x coverage — can capture enriched genetic variations across the entire allele frequency spectrum. In the study, scientists from the University of Hong Kong and elsewhere built a pipeline for the analysis of ulcWGS data for GWAS, applying it to 17,844 embryo samples. They found that a large sample size can increase the accuracy of genotype imputation even at ultra-low coverage. Using the imputed genotypes of 1,744 embryos that were successfully transferred and born with a widespread of gestational ages, the researchers identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. The work, the study's authors write, "provides a foundation for exploring the utilization of an even lower coverage for dissecting genotype-phenotype associations."