Genome-wide linkage of obstructive sleep apnoea and high-density lipoprotein cholesterol in a Filipino family: bivariate linkage analysis of obstructive sleep apnoea

J Sleep Res. 2010 Jun;19(2):349-57. doi: 10.1111/j.1365-2869.2009.00797.x. Epub 2010 Feb 10.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Child
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / genetics*
  • Chromosomes, Human, 19-20 / genetics
  • Family
  • Female
  • Genetic Linkage / genetics
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Insulin / blood
  • Lod Score
  • Male
  • Phenotype
  • Polysomnography
  • Receptors, KIR / genetics
  • Sleep / genetics
  • Sleep / physiology
  • Sleep Apnea, Obstructive / blood
  • Sleep Apnea, Obstructive / genetics*
  • Triglycerides / blood

Substances

  • Cholesterol, HDL
  • Insulin
  • Receptors, KIR
  • Triglycerides
  • Cholesterol