Genotype data from: "Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling."

This data contains genotype data from the GlobalScreeningArray and imputed genotypes from 303 healthy blood donors, generated within a project to investigate pQTLs regulating interferon receptor responses.<br>Results are published in Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling (https://doi.org/10.1371/journal.pgen.1009199)<br><br>Abstract:Interferons (IFNs) are cytokines that are central to the host defence
against viruses and other microorganisms. If not properly regulated,
IFNs may contribute to the pathogenesis of inflammatory autoimmune, or
infectious diseases. To identify genetic polymorphisms regulating the
IFN system we performed an unbiased genome-wide protein-quantitative
trait loci (pQTL) mapping of cell-type specific type I and type II IFN
receptor levels and their responses in immune cells from 303 healthy
individuals. Seven genome-wide significant (p &lt; 5.0E-8) pQTLs were
identified. Two independent SNPs that tagged the multiple sclerosis
(MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively,
were associated with increased levels of IFNAR2 in B and T cells, with
the most prominent effect in IgD^–CD27⁺ memory B
cells. The increased IFNAR2 levels in B cells were replicated in cells
from an independent set of healthy individuals and in MS patients.
Despite increased IFNAR2 levels, B and T cells carrying the
MS-protective alleles displayed a reduced response to type I IFN
stimulation. Expression and methylation-QTL analysis demonstrated
increased mRNA expression of the pseudogene <em>HLA-J</em> in B cells
carrying the MS-protective class I alleles, possibly driven via
methylation-dependent transcriptional regulation. Together these data
suggest that the MS-protective effects of HLA class I alleles are
unrelated to their antigen-presenting function, and propose a previously
unappreciated function of type I IFN signalling in B and T cells in MS
immune-pathogenesis.