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<sup>-3</sup>). 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). ©The Author(s) 2013 Reprints and permissions.
Genetic burden of common variants in progressive and bout-onset multiple sclerosis / Sorosina, Melissa; Brambilla, Paola; Clarelli, Ferdinando; Barizzone, Nadia; Lupoli, Sara; Guaschino, Clara; Osiceanu, Ana Maria; Moiola, Lucia; Ghezzi, Angelo; Coniglio, Gabriella; Patti, Francesco; Mancardi, Gianluigi; Manunta, Paolo; Glorioso, Nicola; Guerini, Franca R; Bergamaschi, Roberto; Perla, Franco; Progresso, ; Progemus, Group; Salvetti, Marco; Martinelli, Vittorio; Cusi, Daniele; Leone, Maurizio; Comi, Giancarlo; D'Alfonso, Sandra; Martinelli-Boneschi, Filippo. - In: MULTIPLE SCLEROSIS. - ISSN 1352-4585. - 20:7(2014), pp. 802-811. [10.1177/1352458513512707]
Genetic burden of common variants in progressive and bout-onset multiple sclerosis
Patti, Francesco;Salvetti,MarcoMembro del Collaboration Group
;LEONE, MAURIZIO;
2014
Abstract
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). ©The Author(s) 2013 Reprints and permissions.| File | Dimensione | Formato | |
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