Genetic burden of common variants in progressive and bout-onset multiple sclerosis

Background:The contribution of genetic variants underlying the susceptibility to different clinical courses of multiple sclerosis (MS) is still unclear.Objective:The aim of the study is to evaluate and compare the proportion of liability explained by common SNPs and the genetic burden of MS-associated SNPs in progressive onset (PrMS) and bout-onset (BOMS) cases.Methods:We estimated the proportion of variance in disease liability explained by 296,391 autosomal SNPs in cohorts of Italian PrMS and BOMS patients using the genome-wide complex trait analysis (GCTA) tool, and we calculated a weighted genetic risk score (wGRS) based on the known MS-associated loci.Results:Our results identified that common SNPs explain a greater proportion of phenotypic variance in BOMS (36.5%±10.1%) than PrMS (20.8%±6.0%) cases, and a trend of decrease was observed when testing primary progressive (PPMS) without brain MRI inflammatory activity (p = 7.9 × 10−3). Similarly, the wGRS and the variance explained by MS-associated SNPs...