RT Journal Article
T1 Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.
A1 Martinón-Torres, Federico
A1 Png, Eileen
A1 Khor, Chiea Chuen
A1 Davila, Sonia
A1 Wright, Victoria J
A1 Sim, Kar Seng
A1 Vega, Ana
A1 Fachal, Laura
A1 Inwald, David
A1 Nadel, Simon
A1 Carrol, Enitan D
A1 Martinón-Torres, Nazareth
A1 Alonso, Sonia Marcos
A1 Carracedo, Angel
A1 Morteruel, Elvira
A1 López-Bayón, Julio
A1 Torre, Andrés Concha
A1 Monge, Cristina Calvo
A1 de Aguilar, Pilar Azcón González
A1 Torné, Elisabeth Esteban
A1 Martínez-Padilla, María Del Carmen
A1 Martinón-Sánchez, José María
A1 Levin, Michael
A1 Hibberd, Martin L
A1 Salas, Antonio
A1 ESIGEM network, 
A1 ESPID meningococcal consortium – UK, 
A1 EUCLIDS consortium members - Imperial College London (www.euclids-project.eu), 
AB 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.
YR 2016
FD 2016-11-02
LK http://hdl.handle.net/10668/10572
UL http://hdl.handle.net/10668/10572
LA en
DS RISalud
RD Apr 15, 2025