TY - UNPB
T1 - Impact of genetic susceptibility to multiple sclerosis on the T cell epigenome: Proximal and distal effects
AU - Roostaei, T.
AU - Klein, H.-U.
AU - Felsky, D.
AU - Kivisäkk, P.
AU - Connor, S.M.
AU - Kroshilina, A.
AU - Yung, C.
AU - Ma, Y.
AU - Kaskow, B.J.
AU - Shao, X.
AU - Rhead, B.
AU - Liu, J.
AU - Patsopoulos, N.
AU - Barcellos, L.F.
AU - Weiner, H.L.
AU - de Jager, P.L.
PY - 2020/7/12
Y1 - 2020/7/12
N2 - We establish a genome-wide map of DNA methylation quantitative trait locus (mQTL) effects in CD4+ T cells isolated from multiple sclerosis (MS) patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both MS susceptibility and local (cis-) DNA methylation. We also identify two distant (trans-) mQTL effects of MS susceptibility loci: (1) a chromosome 16 MS locus affects PRDM8 methylation (a chromosome 4 region not previously associated with MS susceptibility), and (2) the aggregate effect of MS variants in the major histocompatibility complex (MHC, chromosome 6) influences DNA methylation near PRKCA on chromosome 17. Both effects are replicated in independent samples. Overall, we present a new methylome-wide mQTL resource for a key cell type in inflammatory disease research, uncover functional consequences of MS susceptibility variants, including the convergence of MHC risk alleles onto a new gene target involved in predisposition to MS.
AB - We establish a genome-wide map of DNA methylation quantitative trait locus (mQTL) effects in CD4+ T cells isolated from multiple sclerosis (MS) patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both MS susceptibility and local (cis-) DNA methylation. We also identify two distant (trans-) mQTL effects of MS susceptibility loci: (1) a chromosome 16 MS locus affects PRDM8 methylation (a chromosome 4 region not previously associated with MS susceptibility), and (2) the aggregate effect of MS variants in the major histocompatibility complex (MHC, chromosome 6) influences DNA methylation near PRKCA on chromosome 17. Both effects are replicated in independent samples. Overall, we present a new methylome-wide mQTL resource for a key cell type in inflammatory disease research, uncover functional consequences of MS susceptibility variants, including the convergence of MHC risk alleles onto a new gene target involved in predisposition to MS.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85098901200&partnerID=MN8TOARS
U2 - 10.1101/2020.07.11.198721
DO - 10.1101/2020.07.11.198721
M3 - Preprint
BT - Impact of genetic susceptibility to multiple sclerosis on the T cell epigenome: Proximal and distal effects
PB - bioRxiv
ER -