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Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (<jats:italic>P<\/jats:italic>-value\u2009\u2264\u20095\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) in 20 variants located at the <jats:italic>CFH<\/jats:italic> gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR)\u2009=\u20090.62, 95% confidence interval (C.I.)\u2009=\u20090.52\u20130.73; <jats:italic>P<\/jats:italic>-value\u2009=\u20099.62\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup>). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR\u2009=\u20090.64, 95% C.I.)\u2009=\u20090.55\u20130.76, <jats:italic>P-value<\/jats:italic>\u2009=\u20093.25\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of <jats:italic>CFH<\/jats:italic> with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.<\/jats:p>","DOI":"10.1038\/srep35842","type":"journal-article","created":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T12:20:49Z","timestamp":1478089249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies"],"prefix":"10.1038","volume":"6","author":[{"given":"Federico","family":"Martin\u00f3n-Torres","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Png","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiea 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