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Genome‐wide linkage of obstructive sleep apnoea and high‐density lipoprotein cholesterol in a Filipino family: bivariate linkage analysis of obstructive sleep apnoea
Author(s) -
RELF BRONWYN L.,
LARKIN EMMA K.,
TORRES CARINA DE,
BAUR LOUISE A.,
CHRISTODOULOU JOHN,
WATERS KAREN A.
Publication year - 2010
Publication title -
journal of sleep research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.297
H-Index - 117
eISSN - 1365-2869
pISSN - 0962-1105
DOI - 10.1111/j.1365-2869.2009.00797.x
Subject(s) - genetic linkage , respiratory disturbance index , medicine , body mass index , insulin resistance , candidate gene , polysomnography , genome wide association study , locus (genetics) , genetics , biology , obesity , gene , genotype , single nucleotide polymorphism , apnea
Summary 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.