Association of Gastroesophageal Reflux Disease and Anti-reflux Drug Target Genes with Obstructive Sleep Apnea:A Drug-targeted Mendelian Randomization Study / 医药导报

ABSTRACT

Objective To evaluate the causal relationship between gastroesophageal reflux disease(GERD)and obstructive sleep apnea(OSA)using two-sample Mendelian randomization(2SMR)and to identify potentially beneficial drugs and pathways for OSA from GERD treatment options.Methods The 2SMR was used as the primary analysis method,and multivariable Mendelian randomization(MVMR)was used to adjust for the potential impact of obesity on both diseases.Secondly,the DrugBank database was used to search for target genes of anti-reflux drugs used to treat GERD,and the dbSNP database was used to determine the target gene loci to identify the genetic tools of anti-reflux drugs.Significant target genes related to OSA risk were obtained through 2SMR analysis.Finally,the target genes were subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and Gene Ontology(GO)analysis using the DAVID database.Results The genetically predicted risk of GERD was significantly associated with an increased risk of OSA[OR=1.43,95%CI=(1.33,1.54),P=5.29×10-22],and MVMR analysis showed that this result remained robust after adjusting for obesity.Four significant genes,including BCHE,DRD2,GRM5,and PTGER3,were identified,which are related to drugs such as nizatidine,bromperidol,ADX10059,and misoprostol.KEGG analysis identified three pathways.Conclusion GERD increases the risk of developing OSA,and anti-reflux drug targets can provide useful genetic clues for drug development in OSA treatment.