title: Apolipoprotein E and obstructive sleep apnea: evaluating whether a candidate gene explains a linkage peak.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, 11400 Euclid Avenue, Ste. 260, Cleveland, OH 44106-6083, USA. emma.larkin@case.edu
authors.forename: Emma K
authors.initials: EK
authors.lastname: Larkin
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.forename: Joachim
authors.initials: J
authors.lastname: Hallmayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009820:Ohio / Q000453:epidemiology; D015995:Prevalence; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D044465:White People
chemical_list: D001057:Apolipoproteins E