The influence of HLA genetic variation on plasma protein expression.

Autor: Krishna C; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA. Chirag.Krishna@pfizer.com., Chiou J; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., Sakaue S; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Kang JB; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Christensen SM; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., Lee I; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., Aksit MA; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., Kim HI; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., von Schack D; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., Raychaudhuri S; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Ziemek D; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA., Hu X; Pfizer Research and Development, Pfizer Inc., Cambridge, MA, USA. xinli.hu@pfizer.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 31; Vol. 15 (1), pp. 6469. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1038/s41467-024-50583-8
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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