Genome-wide linkage of obstructive sleep apnoea and high-density lipoprotein cholesterol in a Filipino family: bivariate linkage analysis of obstructive sleep apnoea.
Increasing evidence supports an association between obstructive sleep apnoea (OSA) and metabolic syndrome (MeS) in both children and adults, suggesting a genetic component. However, the genetic relationship between the diseases remains unclear. We performed a bivariate linkage scan on a single Filipino family with a high prevalence of OSA and MeS to explore the genetic pathways underlying these diseases. A large rural family (n = 50, 50% adults) underwent a 10-cM genome-wide scan. Fasting blood was used to measure insulin, triglycerides, total cholesterol and high density lipoprotein (HDL) cholesterol. Attended overnight polysomnography was used to quantify the respiratory disturbance index (RDI), a measure of sleep apnoea. Body mass index z-scores and insulin resistance scores were calculated. Bivariate multipoint linkage analyses were performed on RDI and MeS components. OSA prevalence was 46% (n = 23; nine adults, 14 children) in our participants. MeS phenotype was present in 40% of adults (n = 10) and 48% of children (n = 12). Linkage peaks with a logarithm of odds (LOD) score >3 were demonstrated on chromosome 19q13.4 (LOD = 3.04) for the trait pair RDI and HDL cholesterol. Candidate genes identified in this region include the killer cell immunoglobulin-like receptor genes. These genes are associated with modulating inflammatory responses in reaction to cellular stress and initiation of atherosclerotic plaque formation. We have identified a novel locus for genetic links between RDI and lipid factors associated with MeS in a chromosomal region containing genes associated with inflammatory responses.
Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia.
Bronwyn L
BL
Relf
Emma K
EK
Larkin
Carina
C
De Torres
Louise A
LA
Baur
John
J
Christodoulou
Karen A
KA
Waters
D000328:Adult; D015992:Body Mass Index; D002648:Child; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D002903:Chromosomes, Human, 19-20 / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008126:Lod Score; D008297:Male; D010641:Phenotype; D017286:Polysomnography; D054340:Receptors, KIR / Q000235:genetics; D012890:Sleep / Q000235:genetics / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D007328:Insulin; D054340:Receptors, KIR; D014280:Triglycerides; D002784:Cholesterol