SLEEP - A Review of Genetic Association Studies of Obstructive Sleep Apnea: Field Synopsis and Meta-Analysis

VOLUME 34, ISSUE 11

REVIEW OF GENETIC ASSOCIATIONS OF OSA
A Review of Genetic Association Studies of Obstructive Sleep Apnea: Field Synopsis and Meta-Analysis

http://dx.doi.org/10.5665/sleep.1376

Vasileia Varvarigou, MD¹^,²; Issa J. Dahabreh, MD³; Atul Malhotra, MD⁴; Stefanos N. Kales, MD, MPH¹^,²

¹Department of Environmental and Occupational Medicine & Epidemiology, Harvard School of Public Health, Boston, MA ; ²Department of Medicine, Occupational Medicine, Cambridge Health Alliance, Cambridge, MA ; ³Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA ; ⁴Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA

Table of Contents

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Study Objectives:

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.

Design:

Systematic literature review and meta-analysis.

Setting:

Genetic association studies.

Patients or Participants:

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.

Interventions:

None

Measurements and 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, 25^th-75^th percentile = 55-151; median number of controls = 79, 25^th-75^th percentile = 58-137), and genetic effects were moderate in magnitude (median OR = 1.15, 25^th-75^th 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.

Citation:

Varvarigou V; Dahabreh IJ; Malhotra A; Kales SN. A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis. SLEEP 2011;34(11):1461-1468.