Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1385-1395 |
| Number of pages | 11 |
| Journal | Multiple Sclerosis Journal |
| Volume | 21 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Oct 2015 |
Keywords
- Autoimmune disease
- Epidemiology
- Genetic risk score
- Genetics
- Human leukocyte antigen
- Italy
- Mediterranean populations
- Multiple sclerosis
- Sardinia
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The burden of multiple sclerosis variants in continental Italians and Sardinians. / Barizzone, N.; Zara, I.; Sorosina, M.; Lupoli, Sara; Porcu, E.; Pitzalis, M.; Zoledziewska, M.; Esposito, F.; Leone, M.; Mulas, A.; Cocco, E.; Ferrigno, Paola; Guerini, F.R.; Brambilla, P.; Farina, G.; Murru, Roberta; Deidda, Francesca; Sanna, S.; Loi, A. M.; Barlassina, C.; Vecchio, D.; Zauli, Andrea; Clarelli, Ferdinando; Braga, D.; Poddie, F.; Cantello, Roberto; Martinelli, V.; Comi, G.; Frau, J.; Lorefice, Lorena; Pugliatti, M.; Rosati, G.; Melis, M.; Marrosu, M. G.; Cusi, Daniele; Cucca, F.; Martinelli-Boneschi, Filippo; D'Alfonso, S.
In: Multiple Sclerosis Journal, Vol. 21, No. 11, 10.2015, p. 1385-1395.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The burden of multiple sclerosis variants in continental Italians and Sardinians
AU - Barizzone, N.
AU - Zara, I.
AU - Sorosina, M.
AU - Lupoli, Sara
AU - Porcu, E.
AU - Pitzalis, M.
AU - Zoledziewska, M.
AU - Esposito, F.
AU - Leone, M.
AU - Mulas, A.
AU - Cocco, E.
AU - Ferrigno, Paola
AU - Guerini, F.R.
AU - Brambilla, P.
AU - Farina, G.
AU - Murru, Roberta
AU - Deidda, Francesca
AU - Sanna, S.
AU - Loi, A. M.
AU - Barlassina, C.
AU - Vecchio, D.
AU - Zauli, Andrea
AU - Clarelli, Ferdinando
AU - Braga, D.
AU - Poddie, F.
AU - Cantello, Roberto
AU - Martinelli, V.
AU - Comi, G.
AU - Frau, J.
AU - Lorefice, Lorena
AU - Pugliatti, M.
AU - Rosati, G.
AU - Melis, M.
AU - Marrosu, M. G.
AU - Cusi, Daniele
AU - Cucca, F.
AU - Martinelli-Boneschi, Filippo
AU - D'Alfonso, S.
N1 - Export Date: 11 May 2017 Correspondence Address: Sanna, S.; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Cittadella Universitaria di MonserratoItaly; email: serena.sanna@irgb.cnr.it Funding details: 2010-0728, Fondazione Cariplo Funding text: This work was supported by the Italian Foundation for Multiple Sclerosis (FISM) [FISM grant Progetto Speciale Immunochip, 2011/R/14]; Fondazione Cariplo [grant number 2010-0728]; HYPERGENES consortium [grant FP7-HEALTH-F4-2007-201550]; InterOmics project [PB05 MIUR-CNR Italian Flagship Project]; the Cassa Risparmio Torino (CRT) Foundation, Turin, Italy; the Sardinian Autonomous Region (L.R. number 7/2009 and grant numbers cRP3-154 and FaReBio2011 'Farmaci e RetiBiotecnologiche di Qualità'). References: Patsopoulos, N.A., Bayer Pharma, M.S., Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci Ann Neurol, 70, pp. 897-912; Sanna, S., Pitzalis, M., Zoledziewska, M., Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis Nat Genet, 42, pp. 495-497; International Multiple Sclerosis Genetics Consortium (IMSGC), Wellcome Trust Case Control Consortium 2, Sawcer, S., Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis Nature, 476, pp. 214-219; International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham, A.H., Patsopoulos, N.A., Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis Nat Genet, 45, pp. 1353-1360; De Jager, P.L., Chibnik, L.B., Cui, J., Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: A weighted genetic risk score Lancet Neurol, 12, pp. 1111-1119; Gourraud, P.A., McElroy, J.P., Caillier, S.J., Aggregation of multiple sclerosis genetic risk variants in multiple and single case families Ann Neurol, 69, pp. 65-74; Isobe, N., Gourraud, P.A., Harbo, H.F., Genetic risk variants in African Americans with multiple sclerosis Neurology, 81, pp. 219-227; Isobe, N., Madireddy, L., Khankhanian, P., An ImmunoChip study of multiple sclerosis risk in African Americans Brain, 138, pp. 1518-1530. , Brain; Novembre, J., Johnson, T., Bryc, K., Genes mirror geography within Europe Nature, 456, pp. 98-101; Marrosu, M.G., Murru, R., Murru, M.R., Dissection of the HLA association with multiple sclerosis in the founder isolated population of sardinia Hum Mol Genet, 10, pp. 1296-2907; Ballerini, C., Guerini, F.R., Rombolà, G., HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe J Neuroimmunol, 150, pp. 178-185; Pugliatti, M., Rosati, G., Carton, H., The epidemiology of multiple sclerosis in Europe Eur J Neurol, 13, pp. 700-722; Ristori, G., Cannoni, S., Stazi, M.A., Multiple sclerosis in twins from continental Italy and sardinia: A nationwide study Ann Neurol, 59, pp. 27-34; Hadjixenofontos, A., Gourraud, P.A., Bakthavachalam, V., Enrichment for Northern European-derived multiple sclerosis risk alleles in sardinia Mult Scler; Salvi, E., Kutalik, Z., Glorioso, N., Genome-wide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase Hypertension, 59, pp. 248-255; Corrado, L., Bergamaschi, L., Barizzone, N., Association of the CBLB gene with multiple sclerosis: New evidence from a replication study in an Italian population J Med Genet, 48, pp. 210-211; Coraddu, F., Reyes-Yanez, M.P., Parra, A., HLA associations with multiple sclerosis in the canary islands J Neuroimmunol, 87, pp. 130-135; Allcock, R.J., De La Concha, E.G., Fernandez-Arquero, M., Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster Hum Immunol, 60, pp. 1266-1273; Saruhan-Direskeneli, G., Esin, S., Baykan-Kurt, B., HLA-DR and-DQ associations with multiple sclerosis in Turkey Hum Immunol, 55, pp. 59-65; Carreras-Torres, R., Kundu, S., Zanetti, D., Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe PLoS One, 9; Zhernakova, A., Elbers, C.C., Ferwerda, B., Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection Am J Hum Genet, 86, pp. 970-977; Raj, T., Kuchroo, M., Replogle, J.M., Common risk alleles for inflammatory diseases are targets of recent positive selection Am J Hum Genet, 92, pp. 517-529; Ramos, P.S., Shaftman, S.R., Ward, R.C., Genes associated with SLE are targets of recent positive selection Autoimmune Dis, 2014; Brinkworth, J.F., Barreiro, L.B., The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease Curr Opin Immunol, 31, pp. 66-78; Yarwood, A., Han, B., Raychaudhuri, S., A weighted genetic risk score using all known susceptibility variants to estimate rheumatoid arthritis risk Ann Rheum Dis, 74, pp. 170-176; Romanos, J., Rosen, A., Kumar, V., Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants Gut, 63, pp. 415-422; Clayton, D.G., Prediction and interaction in complex disease genetics: Experience in type 1 diabetes PLo Genet, 5; Jostins, L., Barrett, J.C., Genetic risk prediction in complex disease Hum Mol Genet, 20, pp. R182-R188; Sawcer, S., Ban, M., Wason, J., What role for genetics in the prediction of multiple sclerosis? Ann Neurol, 67, pp. 3-10; Wray, N.R., Yang, J., Goddard, M.E., The genetic interpretation of area under the ROC curve in genomic profiling PLoS Genet, 6; Kilpeläinen, T.O., Qi, L., Brage, S., Physical activit attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children PLoS Med, 8; Langenberg, C., Sharp, S.J., Franks, P.W., Genelifestyle interaction and type 2 diabetes: The EPIC interact case-cohort study PLoS Med, 11; Marigorta, U.M., Gibson, G.A., Simulation study of gene-by-environment interactions in GWAS implies ample hidden effects Front Genet, 5, p. 225; Patel, C.J., Ioannidis, J.P., Studying the elusive environment in large scale JAMA, 311, pp. 2173-2174; Hu, Y., Li, L., Ehm, M.G., The benefits of using genetic information to design prevention trials Am J Hum Genet, 92, pp. 547-557
PY - 2015/10
Y1 - 2015/10
N2 - Background: Recent studies identified > 100 non-HLA (human leukocyte antigen) multiple sclerosis (MS) susceptibility variants in Northern European populations, but their role in Southern Europeans is largely unexplored. Objective: We aimed to investigate the cumulative impact of those variants in two Mediterranean populations: Continental Italians and Sardinians. Methods: We calculated four weighted Genetic Risk Scores (wGRS), using up to 102 non-HLA MS risk variants and 5 HLA MS susceptibility markers in 1691 patients and 2194 controls from continental Italy; and 2861 patients and 3034 controls from Sardinia. We then assessed the differences between populations using Nagelkerke's R2 and the area under the Receiver Operating Characteristic (ROC) curves. Results: As expected, the genetic burden (mean wGRS value) was significantly higher in MS patients than in controls, in both populations. Of note, the burden was significantly higher in Sardinians. Conversely, the proportion of variability explained and the predictive power were significantly higher in continental Italians. Notably, within the Sardinian patients, we also observed a significantly higher burden of non-HLA variants in individuals who do not carry HLA risk alleles. Conclusions: The observed differences in MS genetic burden between the two Mediterranean populations highlight the need for more genetic studies in South Europeans, to further expand the knowledge of MS genetics. © The Author(s), 2015.
AB - Background: Recent studies identified > 100 non-HLA (human leukocyte antigen) multiple sclerosis (MS) susceptibility variants in Northern European populations, but their role in Southern Europeans is largely unexplored. Objective: We aimed to investigate the cumulative impact of those variants in two Mediterranean populations: Continental Italians and Sardinians. Methods: We calculated four weighted Genetic Risk Scores (wGRS), using up to 102 non-HLA MS risk variants and 5 HLA MS susceptibility markers in 1691 patients and 2194 controls from continental Italy; and 2861 patients and 3034 controls from Sardinia. We then assessed the differences between populations using Nagelkerke's R2 and the area under the Receiver Operating Characteristic (ROC) curves. Results: As expected, the genetic burden (mean wGRS value) was significantly higher in MS patients than in controls, in both populations. Of note, the burden was significantly higher in Sardinians. Conversely, the proportion of variability explained and the predictive power were significantly higher in continental Italians. Notably, within the Sardinian patients, we also observed a significantly higher burden of non-HLA variants in individuals who do not carry HLA risk alleles. Conclusions: The observed differences in MS genetic burden between the two Mediterranean populations highlight the need for more genetic studies in South Europeans, to further expand the knowledge of MS genetics. © The Author(s), 2015.
KW - Autoimmune disease
KW - Epidemiology
KW - Genetic risk score
KW - Genetics
KW - Human leukocyte antigen
KW - Italy
KW - Mediterranean populations
KW - Multiple sclerosis
KW - Sardinia
U2 - 10.1177/1352458515596599
DO - 10.1177/1352458515596599
M3 - Article
VL - 21
SP - 1385
EP - 1395
JO - Multiple Sclerosis
JF - Multiple Sclerosis
SN - 1352-4585
IS - 11
ER -