title: A genome-wide association study of chronic otitis media with effusion and recurrent otitis media identifies a novel susceptibility locus on chromosome 2.
abstract: Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10(-4) and 12 imputed SNPs with P < 10(-4) on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10(-5)) on chromosome 2 in the independent otitis media population (P = 4.7 × 10(-5); meta-analysis P = 1.52 × 10(-8)). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10(-7)) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.
authors: Center for Public Health Genomics, University of Virginia, P.O. Box 800717, Charlottesville, VA, USA.
authors: E Kaitlynn
authors: EK
authors: Allen
authors: Wei-Min
authors: WM
authors: Chen
authors: Daniel E
authors: DE
authors: Weeks
authors: Fang
authors: F
authors: Chen
authors: Xuanlin
authors: X
authors: Hou
authors: José L
authors: JL
authors: Mattos
authors: Josyf C
authors: JC
authors: Mychaleckyj
authors: Fernando
authors: F
authors: Segade
authors: Margaretha L
authors: ML
authors: Casselbrant
authors: Ellen M
authors: EM
authors: Mandel
authors: Robert E
authors: RE
authors: Ferrell
authors: Stephen S
authors: SS
authors: Rich
authors: Kathleen A
authors: KA
authors: Daly
authors: Michèle M
authors: MM
authors: Sale
mesh_terms: D002889:Chromosomes, Human, Pair 2; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010033:Otitis Media / Q000235:genetics*; D010034:Otitis Media with Effusion / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012008:Recurrence
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