Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies
Por:
Martinón-Torres F, Png E, Khor CC, Davila S, Wright VJ, Sim KS, Vega A, Fachal L, Inwald D, Nadel S, Carrol ED, Martinón-Torres N, Alonso SM, Carracedo A, Morteruel E, López-Bayón J, Torre AC, Monge CC, de Aguilar PA, Esteban-Torne E, Martínez-Padilla MD, Martinón-Sánchez JM, Levin M, Hibberd ML, Salas A, ESIGEM network, ESPID meningococcal consortium – UK and EUCLIDS consortium members - Imperial College London (www.euclids-project.eu)
Publicada:
2 nov 2016
Categoría:
Multidisciplinary
Resumen:
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 x 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 x 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 x 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.
Filiaciones:
Martinón-Torres F:
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, and GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain
Png E:
Infectious Diseases, Genome Institute of Singapore, Singapore
Khor CC:
Human Genetics, Genome Institute of Singapore, Singapore
Davila S:
Human Genetics, Genome Institute of Singapore, Singapore
Wright VJ:
Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, UK
Sim KS:
Human Genetics, Genome Institute of Singapore, Singapore
Vega A:
Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), and Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
Fachal L:
Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), and Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
Inwald D:
Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, UK
Nadel S:
Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, UK
Carrol ED:
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
Martinón-Torres N:
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, and GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain
Alonso SM:
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, and GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain
Carracedo A:
Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), and Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain
Center of Excellence in Genomic Medicine Research, King Abdulaziaz University, Jeddah, Saudi Arabia
Morteruel E:
Unidad de Cuidados Intensivos Pediátricos (UCIP), Hospital de Cruces, Bilbao, Spain
López-Bayón J:
Unidad de Cuidados Intensivos Pediátricos (UCIP), Hospital de Cruces, Bilbao, Spain
Torre AC:
Unidad de Cuidados Intensivos Pediátricos (UCIP), Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
Monge CC:
Servicio de Pediatría, Hospital de Donostia, San Sebastián, Spain
de Aguilar PA:
Unidad de Cuidados Intensivos Pediátricos (UCIP), Hospital Virgen de las Nieves de Granada, Granada, Spain
Esteban-Torne E:
Unidad de Cuidados Intensivos Pediátricos, Hospital Sant Joan de Deu, Barcelona, Spain
Martínez-Padilla MD:
Unidad de Cuidados Intensivos Pediátricos, Complejo Hospitalario de Jaen, Spain
Martinón-Sánchez JM:
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, and GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain
Levin M:
Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, UK
Hibberd ML:
Infectious Diseases, Genome Institute of Singapore, Singapore
Salas A:
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, and GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain
Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain
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