title: Genome-wide association analysis reveals variants on chromosome 19 that contribute to childhood risk of chronic otitis media with effusion.
abstract: To identify genetic risk factors of childhood otitis media (OM), a genome-wide association study was performed on Finnish subjects, 829 affected children, and 2118 randomly selected controls. The most significant and validated finding was an association with an 80 kb region on chromosome 19. It includes the variants rs16974263 (P = 1.77 × 10(-7), OR = 1.59), rs268662 (P = 1.564 × 10(-6), OR = 1.54), and rs4150992 (P = 3.37 × 10(-6), OR = 1.52), and harbors the genes PLD3, SERTAD1, SERTAD3, HIPK4, PRX, and BLVRB, all in strong linkage disequilibrium. In a sub-phenotype analysis of the 512 patients with chronic otitis media with effusion, one marker reached genome-wide significance (rs16974263, P = 2.92 × 10(-8)). The association to this locus was confirmed but with an association signal in the opposite direction, in a UK family cohort of 4860 subjects (rs16974263, P = 3.21 × 10(-4), OR = 0.72; rs4150992, P = 1.62 × 10(-4), OR = 0.71). Thus we hypothesize that this region is important for COME risk in both the Finnish and UK populations, although the precise risk variants or haplotype background remain unclear. Our study suggests that the identified region on chromosome 19 includes a novel and previously uncharacterized risk locus for OM.
authors.affiliation: Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.|Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Einarsdottir
authors.affiliation: Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.|Department of Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Lena
authors.initials: L
authors.lastname: Hafrén
authors.affiliation: Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: Eira
authors.initials: E
authors.lastname: Leinonen
authors.affiliation: Children's Surgical Centre, Phnom Penh, Cambodia.
authors.forename: Mahmood F
authors.initials: MF
authors.lastname: Bhutta
authors.affiliation: Department of Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Erna
authors.initials: E
authors.lastname: Kentala
authors.affiliation: Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.|Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: Department of Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Petri S
authors.initials: PS
authors.lastname: Mattila
mesh_terms: D002648:Child; D002888:Chromosomes, Human, Pair 19 / Q000737:chemistry*; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005387:Finland; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010034:Otitis Media with Effusion / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012306:Risk; D006113:United Kingdom