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Precise and Cost-Effective Nanopore Sequencing for Post-GWAS Fine-Mapping and Causal Variant Identification.

ABSTRACT: Fine-mapping of interesting loci discovered by genome-wide association study (GWAS) is mandatory to pinpoint causal variants. Traditionally, this fine-mapping is completed through increasing the genotyping density at candidate loci, for which imputation is the current standard approach. Although imputation is a useful technique, it has a number of limitations that impede accuracy. In this work, we describe the development of a precise and cost-effective Nanopore sequencing-based pipeline that provides comprehensive and accurate information at candidate loci to identify potential causal single-nucleotide polymorphisms (SNPs). We demonstrate the utility of this technique via the fine-mapping of a GWAS positive hit comprising a synonymous SNP that is associated with doxorubicin-induced cardiotoxicity. In this work, we provide a proof of principle for the application of Nanopore sequencing in post-GWAS fine-mapping and pinpointing of potential causal SNPs with a minimal cost of just ~$10/100 kb/sample.

SUBMITTER: Magdy T

PROVIDER: S-EPMC7096756 | biostudies-literature |

REPOSITORIES: biostudies-literature

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