Genome-wide association analysis reveals variants on chromosome 19 that contribute to childhood risk of chronic otitis media with effusion

• Published in: Scientific reports Vol. 6; no. 1; p. 33240
• Main Authors: Einarsdottir, Elisabet, Hafrén, Lena, Leinonen, Eira, Bhutta, Mahmood F., Kentala, Erna, Kere, Juha, Mattila, Petri S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-09-2016; Nature Publishing Group
• Subjects: 45/23; 45/61; 45/77; 692/4017; 692/699/249; Association analysis; Child; Children; Chromosome 19; Chromosomes; Chromosomes, Human, Pair 19 - chemistry; Chronic Disease; Cohort Studies; Ear diseases; Eardrum; Effusion; Female; Finland; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Humanities and Social Sciences; Humans; Linkage Disequilibrium; Male; Medicin och hälsovetenskap; multidisciplinary; Otitis media; Otitis Media with Effusion - diagnosis; Otitis Media with Effusion - genetics; Otitis Media with Effusion - pathology; Phenotype; Polymorphism, Single Nucleotide; Recurrence; Risk; Risk factors; Science; United Kingdom; United Kingdom > UK
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep33240

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.