Download A genome-wide association study of chronic otitis media with

A genome-wide association study of chronic otitis media with effusion and recurrent otitis media
identifies a novel susceptibility locus on chromosome 2
Michele Sale1, Wei-Min Chen1, Daniel Weeks2, Fang Chen1, Xuanlin Hou1, E. Kaitlynn Allen1, Jose Mattos1,
Josyf Mychaleckyj1, Fernando Segade3, Margaretha Casselbrant4, Ellen Mandel4, Robert Ferrell2, Stephen
Rich1, Kathleen Daly5
1
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 2Dept Human Genetics, University of
Pittsburgh, Pittsburgh, PA, 3Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, PA, 4Dept
Otolaryngology, Children's Hospital of Pittsburgh, Pittsburgh, PA, 5Dept Otolaryngology, University of Minnesota,
Minneapolis, MN
Objectives: 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). Methods: We genotyped 605
subjects from 143 families with 381 COME/ROM subjects, using the Illumina HumanCNV370-Duo DNA
BeadChip (324,748 SNPs). We performed imputation using MACH software. Forty-eight SNPs were selected
for genotyping in an independent family-based sample: all SNPs with P<10-4 (n=36), and 12 imputed SNPs with
P<10-4 on chromosome 15 (near our strongest signal). To date genotyping for 22 of these 48 SNPs has been
completed. Results: In primary analyses, the strongest association with COME/ROM was on chromosome 15
(P=3.4 x 10-7). For the 22 SNPs tested for replication, only SNP rs10497394, located on chromosome 2, was
significantly associated after Bonferroni correction (uncorrected P=0.00026 in the replication data set). Two
SNPs in adjacent genes (C15orf42 and KIF7) at the initial chromosome 15 locus were marginally associated,
with replication P-values <0.05. Conclusion: We have performed the first GWAS of COME/ROM and have
identified a SNP in a novel locus on chromosome 2 that significantly contributes to COME/ROM susceptibility.
This SNP is within a 400 kb intergenic region, bordered by CDCA7 and SP3, but is only 500 bp downstream of
DNAse I hypersensitive ENCODE regions. The genomic and functional significance of this newly-identified
locus in COME/ROM pathogenesis warrants additional investigation.