A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
07 Feb 2024
07 Feb 2024
Historique:
received:
12
05
2023
accepted:
07
12
2023
medline:
8
2
2024
pubmed:
8
2
2024
entrez:
7
2
2024
Statut:
epublish
Résumé
Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call "Whole Exome Genome Sequencing" (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.
Identifiants
pubmed: 38326393
doi: 10.1038/s41525-024-00390-3
pii: 10.1038/s41525-024-00390-3
doi:
Types de publication
Journal Article
Langues
eng
Pagination
8Informations de copyright
© 2024. The Author(s).
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