title: Significant linkage at chromosome 19q for otitis media with effusion and/or recurrent otitis media (COME/ROM).
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: E Kaitlynn
authors.initials: EK
authors.lastname: Allen
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Hou
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Daly
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
mesh_terms: D002888:Chromosomes, Human, Pair 19; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D010034:Otitis Media with Effusion / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence