Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.862255
Keywords
exome sequencing; eosinophils; association testing; inflammation; UK Biobank
Categories
Funding
- Swedish Research Council [2019-01497]
- Swedish Heart and Lung Foundation [20200687]
- Ake Wiberg Foundation
- Marcus Borgstrom Foundation
- A and M Rudbergs Foundation
- Hedstroms K and O F Foundation
- Swedish Research Council [2019-01497] Funding Source: Swedish Research Council
Ask authors/readers for more resources
This study analyzed 200,000 whole-exome sequences from the UK Biobank cohort and identified 220 genes in 55 genomic regions that are associated with eosinophil count. Among these genes, seven are driven by rare variants and two are considered novel eosinophil loci. These findings provide valuable knowledge about the effect of rare variants on eosinophil count and can aid in the identification of therapeutic targets.
Eosinophils play important roles in the release of cytokine mediators in response to inflammation. Many associations between common genetic variants and eosinophils have already been reported, using single nucleotide polymorphism (SNP) array data. Here, we have analyzed 200,000 whole-exome sequences (WES) from the UK Biobank cohort and performed gene-based analyses of eosinophil count. We defined five different variant weighting schemes to incorporate information on both deleteriousness and frequency. A total of 220 genes in 55 distinct (>10 Mb apart) genomic regions were found to be associated with eosinophil count, of which seven genes (ALOX15, CSF2RB, IL17RA, IL33, JAK2, S1PR4, and SH2B3) are driven by rare variants, independent of common variants identified in genome-wide association studies. Two additional genes, NPAT and RMI1, have not been associated with eosinophil count before and are considered novel eosinophil loci. These results increase our knowledge about the effect of rare variants on eosinophil count, which can be of great value for further identification of therapeutic targets.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available