cad a22 4500 551414545 20191218082259.0 cr unu---uuuuu 181214e20181101xx s 000 0 eng 10.5167/uzh-159332 doi 10.1016/j.cell.2018.09.049 doi (ZORA)oai:www.zora.uzh.ch:159332 610 ddc 30343897 pmid Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk [Elektronische Daten] [Mitja Mitrovič, Nikolaos A Patsopoulos, et al, Roland Martin, Mireia Sospedra, Ilijas Jelcic] openAccess eu-repo Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFNγ biology, and NFκB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS. Clinic for Neurology zora General Biochemistry, Genetics and Molecular Biology zora Mitrovič Mitja joint author Patsopoulos Nikolaos A. joint author et al joint author Martin Roland joint author Sospedra Mireia joint author Jelcic Ilijas joint author Cell 175(6):1679-1687.e7 https://www.zora.uzh.ch/id/eprint/159332/8/1-s2.0-S0092867418312613-main.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/159332/8/1-s2.0-S0092867418312613-main.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Mitrovič Mitja joint author ZORA 700 1- Patsopoulos Nikolaos A. joint author ZORA 700 -- et al joint author ZORA 700 1- Martin Roland joint author ZORA 700 1- Sospedra Mireia joint author ZORA 700 1- Jelcic Ilijas joint author ZORA 773 0- Cell 175(6):1679-1687.e7 SWISSBIB 551414545 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess