title: No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.
abstract: While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.
authors.affiliation: Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.
authors.forename: Koldo
authors.initials: K
authors.lastname: Garcia-Etxebarria
authors.affiliation: Unidad Mixta de Investigación en Genómica y Salud CSISP-UVEG/Institut Cavanilles-Universitat de València, València, Spain; CIBER de Epidemiologia y Salud Pública, Madrid, Spain.
authors.forename: María Alma
authors.initials: MA
authors.lastname: Bracho
authors.affiliation: CIBER de Epidemiologia y Salud Pública, Madrid, Spain; Servicio de Microbiología Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Galán
authors.affiliation: Department of Microbiology, Hospital Universitari Vall d'Hebron (HUVH), Universitat Autònoma de Barcelona (UAB), Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Tomàs
authors.initials: T
authors.lastname: Pumarola
authors.affiliation: CIBER de Epidemiologia y Salud Pública, Madrid, Spain; Instituto de Salud Pública de Navarra, Pamplona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Castilla
authors.affiliation: Department of Microbiology and Immunology, Hospital Clinico Universitario, Valladolid, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Ortiz de Lejarazu
authors.affiliation: Servicio de Microbiología Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Rodríguez-Dominguez
authors.affiliation: Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado-Plataforma de Recursos Biomoleculares y Bioinformaticos-Instituto de Salud Carlos III (CeGen-PRB2-ISCIII), Santiago de Compostela, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Quintela
authors.affiliation: Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Bonet
authors.affiliation: Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Garcia-Garcerà
authors.affiliation: CIBER de Epidemiologia y Salud Pública, Madrid, Spain; Departament de Salut Pública, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Domínguez
authors.affiliation: Unidad Mixta de Investigación en Genómica y Salud CSISP-UVEG/Institut Cavanilles-Universitat de València, València, Spain; CIBER de Epidemiologia y Salud Pública, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: González-Candelas
authors.affiliation: Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Calafell
mesh_terms: D005260:Female; D005787:Gene Frequency; D023281:Genomics; D005838:Genotype; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D012367:RNA, Viral