| Title: | The influence of HLA genetic variation on plasma protein expression |
| Journal: | Nature Communications |
| Published: | 31 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39085222/ |
| DOI: | https://doi.org/10.1038/s41467-024-50583-8 |
| URL: | http://dx.doi.org/10.1038/s41467-024-50583-8 |
Publication 12748
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Abstract
Genetic variation in the human leukocyte antigen (HLA) loci is associated with risk of immune-mediated diseases, but the molecular effects of HLA polymorphism are unclear. Here we examined the effects of HLA genetic variation on the expression of 2940 plasma proteins across 45,330 Europeans in the UK Biobank, with replication analyses across multiple ancestry groups. We detected 504 proteins affected by HLA variants (HLA-pQTL), including widespread trans effects by autoimmune disease risk alleles. More than 80% of the HLA-pQTL fine-mapped to amino acid positions in the peptide binding groove. HLA-I and II affected proteins expressed in similar cell types but in different pathways of both adaptive and innate immunity. Finally, we investigated potential HLA-pQTL effects on disease by integrating HLA-pQTL with fine-mapped HLA-disease signals in the UK Biobank. Our data reveal the diverse effects of HLA genetic variation and aid the interpretation of associations between HLA alleles and immune-mediated diseases.</p>
11 Keywords
- Alleles
- Autoimmune Diseases
- Blood Proteins
- Genetic Predisposition to Disease
- Genetic Variation
- HLA Antigens
- Humans
- Immunity, Innate
- Polymorphism, Single Nucleotide
- United Kingdom
- White People
12 Authors
- Chirag Krishna
- Joshua Chiou
- Saori Sakaue
- Joyce B. Kang
- Stephen M. Christensen
- Isac Lee
- Melis Atalar Aksit
- Hye In Kim
- David von Schack
- Soumya Raychaudhuri
- Daniel Ziemek
- Xinli Hu
2 Applications
| Application ID | Title |
|---|---|
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
| 65851 | Large-scale proteomic profiling to facilitate genetics-guided drug discovery and precision medicine: The UK Biobank - Pharma Proteomics Project (UKB-PPP) |
Enabling scientific discoveries that improve human health