STUDIES OF OBSTRUCTIVE SLEEP APNEA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Evidence from both linkage analyses and association-based analyses has implicated Apoliprotein E (ApoE) as a disease susceptibility locus for obstructive sleep apnea. To further assess the putative role of ApoE in sleep apnea, we performed genotyping, association, and linkage analyses in a cohort assembled to investigate the genetic epidemiology of sleep apnea. Among a subset of the Caucasian families, ten microsatellites, spanning 20 cM, were genotyped in a region near ApoE on chromosome 19 where previous suggestive linkage had been demonstrated using a 9.1-cM genome-wide scan. Haseman-Elston regression analysis, conducted with these fine mapping markers (n=196 sibling pairs, 56 families), showed evidence for linkage to marker AFM210yg9 (p=0.00034), which was increased over that observed with the original scan. ApoE genotyping also was performed on a larger set of data (n=1,211 from 271 families, ages 3-85 years) from the cohort with available DNA. To determine whether the ApoE genotype explains the linkage peak, we included the ApoE genotype as a covariate in regression models. Inclusion of ApoE E2 allele as a covariate reduced the regression coefficient by 18%, suggesting that ApoE does not substantively explain the linkage signal. Finally, we repeated an association-based analysis in the larger sample of 1,211 individuals, and observed a higher prevalence of sleep apnea among individuals with the ApoE E2 allele. Overall, the evidence suggests that there is a disease susceptibility locus for obstructive sleep apnea in the region of ApoE, but ApoE itself is unlikely to be the causative locus.