Genome-wide association study of otitis media in the Finnish population.. FIN-OM-GWAS-2016

To identify genetic risk factors of childhood otitis media (OM), a genome-wide association (GWA) study was performed in 829 affected children treated at the Helsinki University Hospital, Finland. In our cohort, 721 had recurrent acute otitis media (RAOM) and 524 chronic otitis media with effusion (COME). A group of 2118 randomly selected Finnish subjects served as controls. The results were followed up in a UK family cohort of 4860 subjects. The most significant and validated finding was an association with an 80 kb region on chromosome 19. It includes the variants rs16974263 (P = 1.77x10-7, OR = 1.59), rs268662 (P = 1.564x10-6, OR = 1.54), and rs4150992 (P = 3.37x10-6, 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 509 patients with COME, one marker reached genome-wide significance (rs16974263; P = 2.92x10-8). The association with this locus was replicated in the UK cohort (rs16974263 P = 3.21x10-4, OR = 0.72; rs4150992 P = 1.62x10-4, OR = 0.71), but with association in the opposite direction. 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 is the first GWA study of childhood OM to identify a genome-wide significant association, and suggests that the identified region on chromosome 19 includes a novel and previously uncharacterized risk locus for childhood OM.