Bhérer, Claude; Eveleigh, Robert; Trajanoska, Katerina; St-Cyr, Janick; Paccard, Antoine; Nadukkalam Ravindran, Praveen; Caron, Elizabeth; Bader Asbah, Nimara; McClelland, Peyton; Wei, Clare; Baumgartner, Iris; Schindewolf, Marc; Döring, Yvonne; Perley, Danielle; Lefebvre, François; Lepage, Pierre; Bourgey, Mathieu; Bourque, Guillaume; Ragoussis, Jiannis; Mooser, Vincent; ... (2024). A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome. NPJ genomic medicine, 9(8) Springer Nature 10.1038/s41525-024-00390-3
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Angiologie 04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) |
UniBE Contributor: |
Baumgartner, Iris, Schindewolf, Marc, Döring, Yvonne |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2056-7944 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
08 Feb 2024 11:17 |
Last Modified: |
09 Feb 2024 05:59 |
Publisher DOI: |
10.1038/s41525-024-00390-3 |
PubMed ID: |
38326393 |
BORIS DOI: |
10.48350/192680 |
URI: |
https://boris.unibe.ch/id/eprint/192680 |
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