Authors:
Rye MS; Warrington NM; Scaman ESH; Vijayasekaran S; Coates HL; Anderson D; Pennell CE; Blackwell JM; Jamieson SE
Authors notes:
PLoS ONE. 2012;7(10):e48215.1-12
Keywords:
Otitis media, Genome wide association, Phenotype, Raine cohort
Abstract
Otitis media (OM) is a common childhood disease characterised by middle ear inflammation and effusion.
Susceptibility to recurrent acute OM (rAOM; ≥3 episodes of AOM in 6 months) and chronic OM with effusion (COME; MEE ≥3 months) is 40-70% heritable.
Few underlying genes have been identified to date, and no genome-wide association study (GWAS) of OM has been reported.
In a gene-based analysis in VEGAS, BPIFA3 (P Gene = 2×10 -5) and BPIFA1 (P Gene = 1.07×10 -4) in the BPIFA gene cluster on chromosome 20q11.21 were the top hits.
In all, 32 genomic regions show evidence of association in this GWAS, with pathway analysis showing a connection between top candidates and the TGFβ pathway.
However, top and tag-SNP analysis for seven selected candidate genes in this pathway did not replicate in 645 families (793 affected individuals) from the Western Australian Family Study of Otitis Media (WAFSOM).
Lack of replication may be explained by sample size, difference in OM disease severity between primary and replication cohorts or due to type I error in the primary GWAS.
This first discovery GWAS for an OM phenotype has identified CAPN14 and GALNT14 on chromosome 2p23.1 and the BPIFA gene cluster on chromosome 20q11.21 as novel candidate genes which warrant further analysis in cohorts matched more precisely for clinical phenotypes.