Nanopore adaptive sampling combines both targeted and low-pass whole genome sequencing in a single assay
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In the 15 years since the first large-scale genome-wide association study (GWAS), there has been an explosion in the number of diseases and traits with significant associations. These discoveries not only shed light on the biology underlying complex traits but also enable the use of polygenic scores (PGS) to predict phenotypes.
Genotyping arrays have played a crucial role in this by providing a cost-effective method to assay common SNVs in large cohorts. More recently low-pass whole-genome sequencing (lpWGS) in combination with genotype imputation has emerged as an alternative method for GWAS and PGS calculation. However, unlike higher-coverage WGS and targeted sequencing, these technologies are not well-suited to the detection of rare or novel variation, limiting their ability to explore the effects of rare variants and make phenotype predictions based on the full allele-frequency spectrum.
Here we demonstrate that Adaptive Sampling (AS) can be combined with genotype imputation to interrogate both rare and common variation in a single assay.