阻塞性睡眠呼吸暂停和2型糖尿病:一项双向孟德尔随机化研究

Obstructive sleep apnea and type 2 diabetes:a bidirectional Mendelian randomization study

目的使用双向孟德尔随机化(Mendelian randomization,MR)对阻塞性睡眠呼吸暂停(OSA)和2型糖尿病(type 2 diabetes,T2D)的因果关系进行探究。方法OSA的相关遗传数据来自全基因组关联研究(Genome-wide association study,GWAS)中的芬兰基因生物银行(FinnGen Biobank,病例组=16761,对照组=201194),从中筛选出3个单核苷酸多态性(single-nucleotide polymorphism,SNP)作为OSA的工具变量(instrumental variable,IV)。T2D的相关遗传数据来源于GWAS的一项大型荟萃分析(病例组=62892,对照组=596424),从中选取了114个SNP作为T2D的IV。采用逆方差加权(inverse variance weighted,IVW)为主的多种MR方法进行分析。采用MR-Egger等方法对MR分析结果进行敏感性分析,并使用F值统计量对IV进行评估。结果MR结果提示:OSA与T2D的风险增高显著相关[比值比(odds ratio,OR)=2.016,95%置信区间(confidence interval,CI)为1.185~3.429,P<0.05]。而T2D与OSA的发病风险无显著相关性(OR=1.030,95%CI为0.980~1.082,P=0.238)。双向结果均存在异质性(OSA➝T2D,P=1.808×10^(-11);T2D➝OSA,P=1.729×10^(-7)),无水平多效性(OSA➝T2D,P=0.477;T2D➝OSA,P=0.349)。本次所选的OSA和T2D的IV均为强工具变量(OSA:F=20.543;T2D:F=30.117)。结论研究结果支持OSA是T2D发病的危险因素,但并未发现T2D对OSA发病有显著影响。在OSA患者中积极进行血糖监测与糖尿病筛查可能有利于T2D的早期发现和及时干预。

Objective This study aims to explore the causal relationship between obstructive sleep apnea(OSA)and type 2 diabetes(T2D)using bidirectional Mendelian randomization(MR).Methods The genetic data related to OSA were obtained from the FinnGen Biobank(Ncase=16,761,Ncontrol=201,194)in the Genome-wide association study(GWAS).Three single nucleotide polymorphism(SNP)were screened out as instrumental variable(IV)of OSA.The genetic data related to T2D were derived from a large Meta-analysis of GWAS(Ncase=62,892,Ncontrol=596,424),114 SNP were selected as IV of T2D.Multiple MR methods were used for analysis and inverse variance weighted(IVW)was performed as main method.The sensitivity of MR analytic results was analyzed using MR-Egger and other methods,and the IV was evaluated using F-value statistics.Results MR analysis showed that OSA was significantly associated with increased risk of T2D(OR=2.016,95%CI:1.185-3.429,P<0.05).There was no significant relationship between T2D and OSA risk(OR=1.030,95%CI:0.980-1.082,P=0.238).There was heterogeneity in both-way results(OSA➝T2D,P=1.808×10^(-11);T2D➝OSA,P=1.729×10^(-7)),and no horizontal pleiotropy(OSA➝T2D,P=0.477;T2D➝OSA,P=0.349).IV of OSA and T2D-selected in the study were strong instrumental variables(F statistics of OSA=20.543;F statistics of T2D=30.117).Conclusion Our results supported that OSA was a risk factor for T2D,but T2D had no significant impact on the incidence of OSA.Blood glucose monitoring and diabetes screening in OSA patients might be beneficial to the early detection and intervention of T2D.