TY - JOUR
T1 - Genetic burden of common variants in progressive and bout-onset multiple sclerosis
AU - PROGRESSO
AU - PROgnostic GEnetic factors in MUltiple Sclerosis
AU - Sorosina, Melissa
AU - Brambilla, Paola
AU - Clarelli, Ferdinando
AU - Barizzone, Nadia
AU - Lupoli, Sara
AU - Guaschino, Clara
AU - Osiceanu, Ana Maria
AU - Moiola, Lucia
AU - Ghezzi, Angelo
AU - Coniglio, Gabriella
AU - Patti, Francesco
AU - Mancardi, Gianluigi
AU - Manunta, Paolo
AU - Glorioso, Nicola
AU - Guerini, Franca R.
AU - Bergamaschi, Roberto
AU - Perla, Franco
AU - Martinelli, Vittorio
AU - Cusi, Daniele
AU - Leone, Maurizio
AU - Comi, Giancarlo
AU - D'Alfonso, Sandra
AU - Martinelli-Boneschi, Filippo
AU - Esposito, F.
AU - Liberatore, G.
AU - Rodegher, M.
AU - Rossi, P.
AU - Radaelli, M.
AU - Colombo, B.
AU - Annovazzi, P.
AU - Capra, R.
AU - Amato, M. P.
AU - Nacmias, B.
AU - D’Ambrosio, A.
AU - Tedeschi, G.
AU - Cavalla, P.
AU - D’Amico, E.
AU - Galimberti, D.
AU - Scarpini, E.
AU - Atzori, M.
AU - Gallo, P.
AU - Bucello, S.
AU - Grimaldi, L.
AU - Capello, E.
AU - Naldi, P.
AU - Di Sapio, A.
AU - Caputo, D.
AU - Rosso, G.
AU - Cordera, S.
AU - Cavallo, R.
N1 - Funding Information:
Dr Patti has served Bayer Schering, Biogen Idec, Merck Serono, Novartis and Sanofi-Aventis as advisory board member; he further received honoraria for speaking activities by Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Aventis and Teva; and he has received a grant for research activities by FISM and partial technical support by Reload Onlus Association.
Funding Information:
Dr Moiola has received speaking honoraria and a travel grant from Merck Serono and Biogen Idec.
Funding Information:
Dr Martinelli-Boneschi has received speaker honoraria and funding for travel from Sanofi-Aventis, Biogen-Dompè. He receives research support from the Giovani Ricercatori 2007 grant (D.lgs 502/92) from the Italian Ministry of Health, Fondazione Cariplo, and Fondazione Italiana Sclerosi Multipla.
PY - 2014/6/1
Y1 - 2014/6/1
N2 - 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).
AB - 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).
KW - Genome-wide association study
KW - Heritability
KW - Multiple sclerosis
KW - Primary progressive
KW - Relapsing-remitting
UR - http://www.scopus.com/inward/record.url?scp=84902164518&partnerID=8YFLogxK
U2 - 10.1177/1352458513512707
DO - 10.1177/1352458513512707
M3 - Article
SN - 1352-4585
VL - 20
SP - 802
EP - 811
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 7
ER -