Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

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Martinón-Torres, F, Png, E, Khor, CC, Davila, S, Wright, VJ, Sim, KS, Vega, A, Fachal, L, Inwald, D, Nadel, S et al (show 82 more authors) , Carrol, ED ORCID: 0000-0001-8357-7726, Martinón-Torres, N, Alonso, SM, Carracedo, A, Morteruel, E, López-Bayón, J, Torre, AC, Monge, CC, De Aguilar, PAG, Torné, EE, Martínez-Padilla, MDC, Martinón-Sánchez, JM, Levin, M, Hibberd, ML, Salas, A, Gómez-Carballa, A, Cebey, M, Sánchez, NG, Calle, IR, Grande, AJ, Pardo-Seco, J, Barral-Arca, R, Pischedda, S, Currás-Tuala, MJ, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Sánchez, FP, De La Cruz Moreno, J, Millán Miralles, ML, García Rodríguez, JL, García, SR, Doce, AH, Barba, ÁF, Pallares, MO, Romero, AR, Muñoz Bonet, JI, Cancela, MS, Bergara, EO, Arriortua, AB, Navarro Gómez, ML, Fernández, MS, Martínez, XA, Ortega, ÁC, Rosso, SP, Caballero Macarrón, CP, Menchón, NM, Sánchez, FG, Garzón, MGR, García, MDMB, Sánchez Granados, JM, Ayestarán, OS, Payo, R, Palazón, SC, León León, MC, Dominguez, SR, Villanueba, DA, Alonso Martín, JA, Orayen, CG, Iturbe, EB, Alonso Salas, MT, Fernández, IQ, Booy, R, Coin, LJM, Eleftherohorinou, H, Faust, S, Galassini, R, Habibi, P, Haralambous, E, Kroll, S, Langford, P, Pathan, N, Pollard, AJ, Abdulla, F, Agapow, P, Bellos, E, Hamilton, S, Herberg, JA, Hoggart, C, Kaforou, M, Mashbat, M, Mustafa, S and Sancho-Shimizu, V (2016) Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies Scientific Reports, 6 (1). 35842-. ISSN 2045-2322, 2045-2322

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Abstract

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. 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 (P-value ≤ 5 × 10^-8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10^-9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10^-8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

Item Type:	Article
Uncontrolled Keywords:	ESIGEM network, ESPID meningococcal consortium – UK, EUCLIDS consortium members - Imperial College London (www.euclids-project.eu), Humans, Meningococcal Infections, Complement Factor H, Odds Ratio, Genotype, Polymorphism, Single Nucleotide, Databases, Factual, Spain, Immunity, Innate, Genome-Wide Association Study, Genetic Loci, White People
Depositing User:	Symplectic Admin
Date Deposited:	07 Nov 2016 07:57
Last Modified:	01 Mar 2026 05:03
DOI:	10.1038/srep35842
Open Access URL:	http://www.nature.com/articles/srep35842
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3004384
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