Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome.

Of those, 38,776 (95%) showed the same direction of effect, 33,128 (81%) also had a nominally significant p value ( p < 0.05), and 25,544 (63%) had an FDR-adjusted p < 0.05 in the BLUEPRINT data (Fig. 1b , Supplementary Data 1 ).

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However, assessing the functional effects of the trans -mCpGs using the BLUEPRINT data, we observed a highly significant positive association between cg19409579 methylation level and PRDM8 mRNA expression in naïve CD4 + T cells ( n = 127, ρ = 0.49, association p value adjusted for age and sex = 4.7 × 10 −9 , Fig. 3c ). cis and trans DNA methylation effects of an MS susceptibility polygenic score for the MHC The MHC has a complex long-range LD structure and harbors 32 independent genome-wide significant associations with MS 2 , including the haplotype with the largest MS-associated risk, HLA-DRB1*1501 .

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