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

Tarek Magdy, Hui–Hsuan –H Kuo, Paul W. Burridge*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number100971
JournaliScience
Volume23
Issue number4
DOIs
StatePublished - Apr 24 2020

Keywords

  • Genomic Analysis
  • Genomics
  • Omics
  • Pharmacoinformatics

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Precise and Cost-Effective Nanopore Sequencing for Post-GWAS Fine-Mapping and Causal Variant Identification'. Together they form a unique fingerprint.

Cite this