Copy number variations and their effect on the plasma proteome.

Schmitz D, Li Z, Lo Faro V, Rask-Andersen M, Ameur A, Rafati N, Johansson Å

Genetics - (-) - [2023-10-04; online 2023-10-04]

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 sub-cohort (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, five CNVs could be perfectly validated using long-read sequencing, including a CNV which was associated to 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.

Bioinformatics Support and Infrastructure [Collaborative]

Bioinformatics Support for Computational Resources [Service]

Bioinformatics Support, Infrastructure and Training [Collaborative]

NGI Long read [Collaborative]

NGI Uppsala (Uppsala Genome Center) [Collaborative]

National Genomics Infrastructure [Collaborative]

PubMed 37793096

DOI 10.1093/genetics/iyad179

Crossref 10.1093/genetics/iyad179

pii: 7289162

Publications 9.5.0