Large-scale integration of the plasma proteome with genetics and disease
- 2 December 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 53 (12), 1712-1721
- https://doi.org/10.1038/s41588-021-00978-w
Abstract
The plasma proteome can help bridge the gap between the genome and diseases. Here we describe genome-wide association studies (GWASs) of plasma protein levels measured with 4,907 aptamers in 35,559 Icelanders. We found 18,084 associations between sequence variants and levels of proteins in plasma (protein quantitative trait loci; pQTL), of which 19% were with rare variants (minor allele frequency (MAF) < 1%). We tested plasma protein levels for association with 373 diseases and other traits and identified 257,490 associations. We integrated pQTL and genetic associations with diseases and other traits and found that 12% of 45,334 lead associations in the GWAS Catalog are with variants in high linkage disequilibrium with pQTL. We identified 938 genes encoding potential drug targets with variants that influence levels of possible biomarkers. Combining proteomics, genomics and transcriptomics, we provide a valuable resource that can be used to improve understanding of disease pathogenesis and to assist with drug discovery and development.Keywords
This publication has 57 references indexed in Scilit:
- Variant ofTREM2Associated with the Risk of Alzheimer's DiseaseThe New England Journal of Medicine, 2013
- Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunityNature Genetics, 2012
- Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human bloodNucleic Acids Research, 2011
- The Icelandic Cancer Project – a population-wide approach to studying cancerNature Reviews Cancer, 2004
- Trans -Suppression of Misfolding in an Amyloid DiseaseScience, 2001
- Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus)Mammalian Genome, 2001
- Human beta-defensin-2The International Journal of Biochemistry & Cell Biology, 1999
- Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor geneNature, 1996
- Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation.Genes & Development, 1993
- The physicochemical basis of cholesterol gallstone formation in manJCI Insight, 1968