Obstructive Sleep Apnea Susceptibility Genes in Chinese Population: A Field Synopsis and Meta-Analysis of Genetic Association Studies.

Jinxian Sun,Chunlin Tu,Jianrong Hu,Huajun Xu,Anyuan Zhong,Shahrad Taheri

doi:10.1371/journal.pone.0135942

Abstract

BackgroundEpidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). However, the results of these studies have been inconclusive. In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA-susceptible genes in Chinese population, to perform a more precise evaluation of the association.MethodsVarious databases (i.e., PubMed, EMBASE, HuGE Navigator, Wanfang and CNKI) were searched to identify all eligible GAS-related variants associated with susceptibility to OSA. The generalized odds ratio metric (ORG) and the odds ratio (OR) of the allele contrast were used to quantify the impact of genetic variants on the risk of OSA. Cumulative and recursive cumulative meta-analyses (CMA) were also performed to investigate the trend and stability of effect sizes as evidence was accumulated.ResultsThirty-two GAS evaluating 13 polymorphisms in 10 genes were included in our meta-analysis. Significant associations were derived for four polymorphisms either for the allele contrast or for the ORG. The variants TNF-α-308G/A, 5-HTTLPR, 5-HTTVNTR, and APOE showed marginal significance for ORG (95% confidence interval [CI]): 2.01(1.31–3.07); 1.31(1.09–1.58); 1.85(1.16–2.95); 1.79(1.10–2.92); and 1.79(1.10–2.92) respectively. In addition, the TNF-α-308G/A, 5-HTTLPR, and 5-HTTVNTR variants showed significance for the allele contrast: 2.15(1.39–3.31); 2.26(1.58–3.24); 1.32(1.12–1.55); and 1.86(1.12–3.08) respectively. CMA showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant.ConclusionsTNF-α, 5-HTT, and APOE genes can all be proposed as OSA-susceptibility genes in Chinese population. Genome-wide association studies (GWAS) are therefore urgently needed to confirm our findings within a larger sample of OSA patients in China.

Highlights

Obstructive sleep apnea (OSA) is one of the most common sleep breathing disorders, affecting approximately 2% of females and 4% of males in Western countries [1]
cumulative meta-analyses (CMA) showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant
tumor necrosis factor (TNF)-α, 5-HTT, and apolipoprotein E (APOE) genes can all be proposed as OSA-susceptibility genes in Chinese population

Summary

Introduction

Obstructive sleep apnea (OSA) is one of the most common sleep breathing disorders, affecting approximately 2% of females and 4% of males in Western countries [1]. It is generally believed that OSA is a complex disorder involving multiple traits, and incorporating a hereditary component [6,7]. Both genetic factors and environmental exposures can contribute to the development of OSA [7]. Epidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). The results of these studies have been inconclusive In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA-susceptible genes in Chinese population, to perform a more precise evaluation of the association

Methods

Results

Conclusion