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Open Access Research article

Significant linkage at chromosome 19q for otitis media with effusion and/or recurrent otitis media (COME/ROM)

Wei-Min Chen12, E Kaitlynn Allen13, Josyf C Mychaleckyj12, Fang Chen1, Xuanlin Hou1, Stephen S Rich124, Kathleen A Daly6 and Michèle M Sale145*

Author Affiliations

1 Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA

2 Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA

3 Department of Biology, University of Virginia, Charlottesville, VA 22908, USA

4 Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA

5 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA

6 Department of Otolaryngology, University of Minnesota, Minneapolis MN 55455, USA

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BMC Medical Genetics 2011, 12:124  doi:10.1186/1471-2350-12-124

Published: 26 September 2011

Abstract

Background

In previous analyses, we identified a region of chromosome 19 as harboring a susceptibility locus for chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). Our aim was to further localize the linkage signal and ultimately identify the causative variant or variants. We followed up our previous linkage scan with dense SNP genotyping across in a 5 Mb region. A total of 607 individuals from 139 families, including 159 affected sib pairs and 62 second-degree affected relative pairs, were genotyped at 1,091 SNPs. We carried out a nonparametric linkage analysis, modeling marker-to-marker linkage disequilibrium.

Results

The maximum log of the odds (LOD) score increased to 3.75 (P = 1.6 × 10-5) at position 63.4 Mb, with a LOD-1 support interval between 61.6 Mb and 63.8 Mb, providing significant evidence of linkage between this region and COME/ROM. The support interval contains over 90 known genes, including several genes involved in the inflammasome protein complex, a key regulator of the innate immune response to harmful exogenous or endogenous stimuli. Parametric linkage analysis suggests that for a sib of an affected individual, the recurrence risk of COME/ROM due to this linkage region is twice the recurrence risk in the population. We examined potential associations between the SNPs genotyped in this region and COME/ROM, however none provided evidence for association.

Conclusion

This study has refined the 19q region of linkage with COME/ROM, and association results suggest that the linkage signal may be due to rare variants.

Keywords:
Linkage; fine mapping; otolaryngology