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

Tina Roostaei, Hans-Ulrich Klein, Yiyi Ma, Daniel Felsky, Pia Kivisäkk, Sarah M. Connor, Alexandra Kroshilina, Christina Yung, Belinda J. Kaskow, Xiaorong Shao, Brooke Rhead, José M. Ordovás, Devin M. Absher, Donna K. Arnett, Jia Liu, Nikolaos Patsopoulos, Lisa F. Barcellos, Howard L. Weiner and Philip L. De Jager ()
Additional contact information
Tina Roostaei: Columbia University Irving Medical Center
Hans-Ulrich Klein: Columbia University Irving Medical Center
Yiyi Ma: Columbia University Irving Medical Center
Daniel Felsky: University of Toronto
Pia Kivisäkk: Massachusetts General Hospital
Sarah M. Connor: Columbia University Irving Medical Center
Alexandra Kroshilina: Columbia University Irving Medical Center
Christina Yung: Columbia University Irving Medical Center
Belinda J. Kaskow: Brigham and Women’s Hospital, Harvard Medical School
Xiaorong Shao: University of California
Brooke Rhead: University of California
José M. Ordovás: Tufts University
Devin M. Absher: HudsonAlpha Institute for Biotechnology
Donna K. Arnett: University of Kentucky
Jia Liu: City University of New York
Nikolaos Patsopoulos: Brigham and Women’s Hospital, Harvard Medical School
Lisa F. Barcellos: University of California
Howard L. Weiner: Brigham and Women’s Hospital, Harvard Medical School
Philip L. De Jager: Columbia University Irving Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Identifying the effects of genetic variation on the epigenome in disease-relevant cell types can help advance our understanding of the first molecular contributions of genetic susceptibility to disease onset. Here, we establish a genome-wide map of DNA methylation quantitative trait loci in CD4+ T-cells isolated from multiple sclerosis patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both multiple sclerosis susceptibility and local DNA methylation. We also identify two distant methylation effects of multiple sclerosis susceptibility loci: a chromosome 16 locus affects PRDM8 methylation (a chromosome 4 region not previously associated with multiple sclerosis), and the aggregate effect of multiple sclerosis-associated variants in the major histocompatibility complex influences DNA methylation near PRKCA (chromosome 17). Overall, we present a new resource for a key cell type in inflammatory disease research and uncover new gene targets for the study of predisposition to multiple sclerosis.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27427-w

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DOI: 10.1038/s41467-021-27427-w

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