Unveiling the mystery: Investigating the debate surrounding mitochondrial DNA copy number and Sjögren syndrome using Mendelian randomization analysis

Numerous studies have investigated the relationship between mitochondrial DNA (mtDNA) copy number and Sjögren syndrome (SS). However, the conclusions remain inconclusive, with conflicting findings. The genome-wide association study summary statistics for mtDNA copy number were obtained from 2 sources: a cohort of 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the UK Biobank, and a dataset of 395,718 UK Biobank participants. Additionally, we obtained 2 sets of genome-wide association study summary statistics for SS through datasets from FinnGen and the UK Biobank, involving a total of 809,836 participants. Furthermore, we conducted a two-sample bidirectional Mendelian randomization analysis, primarily utilizing the inverse variance weighted method, complemented by 4 other validation methods, to explore the association between mtDNA copy number and SS. Following our comprehensive investigation, no discernible causal relationship was identified between mtDNA copy number and SS in either the training or validation cohorts (inverse variance weighted, P > .05). Similarly, the reverse Mendelian randomization analysis yielded negative results (inverse variance weighted, P > .05). Furthermore, all analyses indicated an absence of horizontal pleiotropy or heterogeneity. Our analysis revealed no causal relationship between mtDNA copy number and SS.