Chronic and recurrent otitis media: A genome scan for susceptibility loci

Kathleen A. Daly, W. Mark Brown, Fernando Segade, Donald W. Bowden, Bronya J. Keats, Bruce R Lindgren, Samuel C Levine, Stephen S. Rich

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Otitis media (OM) is the most common childhood disease. Almost all children experience at least one episode, but morbidity is greatest in children who experience chronic/recurrent OM (COME/ROM). There is mounting evidence that COME/ROM clusters in families and exhibits substantial heritability. Subjects who had tympanostomy tube surgery for COME/ROM (probands) and their families were recruited for the present study, and an ear examination was performed, without knowledge of the subject's history, to determine presence of OM sequelae. In addition, tympanometric testing was performed at three frequencies (226, 630 or 710, and 1,400 Hz) to detect abnormal middle-ear mechanics, and hearing was screened at 20 dB for the speech frequencies. Of these families, 121 had at least two individuals who had received the diagnosis of COME/ROM (364 affected and genotyped individuals), of whom 238 affected and informative relative pairs were used for analyses. Single-point nonparametric linkage analysis provided evidence of linkage of COME/ROM to chromosome 10q at marker D10S212 (LOD 3.78; P = 3.0 × 10-5) and to chromosome 19q at marker D19S2S4 (LOD 2.61; P = 5.3 × 10-4). Analyses conditional on support for linkage at chromosomes 10q and 19q resulted in a significant increase in LOD score support on chromosome 3p (between markers D3S4S4S and D3S1259). These results suggest that risk of COME/ROM is determined by interactions between genes that reside in several candidate regions of the genome and are probably modulated by other environmental risk factors.

Original languageEnglish (US)
Pages (from-to)988-997
Number of pages10
JournalAmerican Journal of Human Genetics
Volume75
Issue number6
DOIs
StatePublished - Dec 2004

Bibliographical note

Funding Information:
We are grateful to the numerous individuals and families who donated their time and resources. We thank Michelle Bochert, Jennifer Palmer, Kendra Herrell, Judy Monroe, Norrita Rech, Kim Canfield, and Heather Nelson, for support in patient recruitment and collection; Chris Valis and Mindy Cox, for analytic support; and William Oetting and Richard King, for molecular genetics support. The genome scan was performed by the CIDR. The research was supported by National Institutes of Health grants NIDCD R01 DC03166, P30 DC04660, P01 DC00133, and NCRR M01 RR00400. Appendix A

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