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

Melissa Sorosina, Paola Brambilla, Ferdinando Clarelli, Nadia Barizzone, Sara Lupoli, Clara Guaschino, Ana Maria Osiceanu, Lucia Moiola, Angelo Ghezzi, Gabriella Coniglio, Francesco Patti, Gianluigi Mancardi, Paolo Manunta, Nicola Glorioso, Franca R. Guerini, Roberto Bergamaschi, Franco Perla, Vittorio Martinelli, Daniele Cusi, Maurizio LeoneGiancarlo Comi, Sandra D'Alfonso, Filippo Martinelli-Boneschi

Research output: Contribution to journalArticlepeer-review


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 MSassociated SNPs were higher in BOMS than PPMS in males (wGRS: 6.63 vs 6.51, p = 0.04; explained variance: 4.8%±1.5% vs 1.7%±0.6%; p = 0.05).

Original languageEnglish
Pages (from-to)802-811
Number of pages10
JournalMultiple Sclerosis Journal
Issue number7
Publication statusPublished - 2014


  • Genome-wide association study
  • Heritability
  • Multiple sclerosis
  • Primary progressive
  • Relapsing-remitting

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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