title: A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis.
abstract: OBJECTIVE
  Obstructive sleep apnea (OSA) is a multifactorial disorder with a heritable component. We performed a field synopsis of genetic association studies of OSA to synthesize the available evidence.
  
  
  METHODS
  Systematic literature review and meta-analysis.
  
  
  METHODS
  Genetic association studies.
  
  
  METHODS
  We searched multiple databases to identify studies of non-HLA genetic associations in OSA. We assessed the power of the primary studies to identify odds ratios (OR) in a plausible range and performed random effects meta-analyses for genetic associations investigated by at least 3 studies. We explored the consistency of the findings between population- and family-based studies.
  
  
  METHODS
  None
  
  
  RESULTS
  We identified a total of 31 population-based case-control studies reporting allele-frequency data on 48 polymorphism-OSA associations. Sample sizes were generally small (median number of cases = 102, 25th-75th percentile = 55-151; median number of controls = 79, 25th-75th percentile = 58-137), and genetic effects were moderate in magnitude (median OR = 1.15, 25th-75th percentile = 0.89-1.40). Studies were severely underpowered to detect ORs as high as 2; only eight comparisons (in 6 studies) had more than 90% power to identify a genetic effect of that magnitude at its current sample size. Four genetic associations had been investigated in ≥ 3 studies: TNFA (-308 A/G) rs1800629, ACE I/D, APOE ε2, and APOE ε4. Only TNFA rs1800629 was significantly associated with OSA under an allele frequency model (3 studies, odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.26-2.61). These results were robust to alternative genetic models; findings for APOE variants were consistent with those from family-based studies.
  
  
  CONCLUSIONS
  The developing field of OSA genetics is currently dominated by small and underpowered investigations. Promising findings regarding TNFA rs1800629 need to be replicated in larger studies using more comprehensive genotyping methods.
authors: Department of Environmental and Occupational Medicine & Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors: Vasileia
authors: V
authors: Varvarigou
authors: Issa J
authors: IJ
authors: Dahabreh
authors: Atul
authors: A
authors: Malhotra
authors: Stefanos N
authors: SN
authors: Kales
mesh_terms: D053329:Apolipoprotein E2 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D020181:Sleep Apnea, Obstructive / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D014409:Tumor Necrosis Factor-alpha; D007703:Peptidyl-Dipeptidase A