Objective  To analyze the causal relationship between immune cells and gastroesophageal reflux disease (GERD) by bidirectional Mendelian randomization (MR) method.

Methods  The genome-wide association study (GWAS) database was used for data mining. The positive MR exposure factor was 731 immune cell features, and the outcome factor was GERD. The reverse MR exposure factor was GERD, and the outcome factor was meaningful immune cell features in the positive MR results to rule out the interference of reverse causality. Five methods, including inverse variance weighted (IVW), were used for MR analysis. And the heterogeneity test, horizontal pleiotropy analysis and sensitivity analysis were also performed.

Results  There were three immune cell features that were causally related to GERD, namely  IgD-CD27-%B cell[OR=0.960, 95%CI(0.940, 0.981), P<0.001], FSC-A on NK[OR=0.955, 95%CI (0.932, 0.979), P<0.001], and EM CD4+%CD4+[OR=1.056, 95%CI(1.025, 1.087), P<0.001].

Conclusion  In this study, bidirectional MR analysis was used to reduce reverse causality, and the causal relationship between three immunophenotypes and GERD was revealed genetically, which provides a new perspective for the study of the immune mechanism of GERD, and provides a theoretical basis for the early diagnosis and immunotherapy of the  disease.

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