Causal association between years of schooling and the risk of traumatic brain injury: A two-sample mendelian randomization analysis

Objective To investigate whether the number of years of schooling are causally associated traumatic brain injury (TBI). We aimed to investigate whether the number of years of schooling are causally associated TBI. Methods We investigate the prospective causal effect of years of schooling on TBI using summary statistical data. The statistical dataset comprising years of schooling (n = 293,723) from genome-wide association studies (GWASs) deposited in the UK Biobank was used for exposure. We used the following GWAS available in the FinnGen dataset: individuals with TBI (total = 13,165; control = 136,576; number of single nucleotide polymorphisms [SNPs] = 16,380,088). Results Seventy significant genome-wide SNPs from GWAS datasets with annotated years of schooling were selected as instrumental variables. The inverse variance weighted method results supported a causal relationship between years of schooling and TBI (odds ratio (OR), 0.78; 95 % confidence interval (CI), 0.62–0.98; P = 0.029). MR-Egger regression showed that polydirectionality was unlikely to bias the results (intercept = 0.007, SE = 0.01, P = 0.484) and demonstrated no causal relationship between years of schooling and TBI (OR, 0.52; 95%CI, 0.17–1.64; P = 0.270). The weighted median method revealed a causal relationship with TBI (OR, 0.73; 95%CI, 0.55–0.98; P = 0.047). A Cochran's Q test and funnel plot did not show heterogeneity nor asymmetry, indicating no directional pleiotropy. Conclusions The current investigation yields substantiation of a causal association between years of schooling and TBI development. More years of schooling may be causally associated with a reduced risk of TBI, which has implications for clinical and public health practices and policies.