Copy number variations and their effect on the plasma proteome.
copy number variation
long-read sequencing
plasma proteome
whole-genome sequencing
Journal
Genetics
ISSN: 1943-2631
Titre abrégé: Genetics
Pays: United States
ID NLM: 0374636
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
received:
25
08
2023
accepted:
15
09
2023
medline:
7
12
2023
pubmed:
4
10
2023
entrez:
4
10
2023
Statut:
ppublish
Résumé
Structural variations, including copy number variations (CNVs), affect around 20 million bases in the human genome and are common causes of rare conditions. CNVs are rarely investigated in complex disease research because most CNVs are not targeted on the genotyping arrays or the reference panels for genetic imputation. In this study, we characterize CNVs in a Swedish cohort (N = 1,021) using short-read whole-genome sequencing (WGS) and use long-read WGS for validation in a subcohort (N = 15), and explore their effect on 438 plasma proteins. We detected 184,182 polymorphic CNVs and identified 15 CNVs to be associated with 16 proteins (P < 8.22×10-10). Of these, 5 CNVs could be perfectly validated using long-read sequencing, including a CNV which was associated with measurements of the osteoclast-associated immunoglobulin-like receptor (OSCAR) and located upstream of OSCAR, a gene important for bone health. Two other CNVs were identified to be clusters of many short repetitive elements and another represented a complex rearrangement including an inversion. Our findings provide insights into the structure of common CNVs and their effects on the plasma proteome, and highlights the importance of investigating common CNVs, also in relation to complex diseases.
Identifiants
pubmed: 37793096
pii: 7289162
doi: 10.1093/genetics/iyad179
pmc: PMC10697815
pii:
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Foundation for Strategic Research and the European Commission FP6
Organisme : Science for Life Laboratory
Organisme : Swedish Genomes Program
Organisme : Knut and Alice Wallenberg Foundation
Organisme : Marcus Borgström's and Hedström's foundations
Organisme : Swedish Research Council
ID : 2019-01497
Organisme : Swedish Heart-Lung
ID : 20200687
Organisme : Swedish Cancer Society
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.
Déclaration de conflit d'intérêts
Conflict of interest M.R.A. has performed remunerated consulting services for Olink Proteomics, Uppsala, Sweden. D.S., Z.L., V.L.F., A.A., N.R., and Å.J. declare no competing interests.
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