Spinal pain and major depression in a military cohort: bias analysis of dependent misclassification in electronic medical records.

BACKGROUND: Spinal pain and major depression are prevalent conditions in adult populations and are particularly impactful in the military. However, the temporal relationship between these two conditions remains poorly understood. METHODS: Using data extracted from electronic medical records, we assessed the association between incident diagnoses of spinal pain and major depression in a cohort of 48,007 Canadian Armed Forces personnel followed from January 2017 to August 2018. We used multivariate Poisson regression to measure the association between the period prevalence of these two conditions. We used probabilistic bias modelling to correct our estimates for misclassification of spinal pain and major depression. RESULTS: After correcting for misclassification with probabilistic bias modelling, subjects newly diagnosed with spinal pain during the study period were 1.41 times (95% interval 1.25, 1.59) more likely also to be diagnosed with incident major depression, and personnel newly diagnosed with major depression were 1.28 times (95% interval 1.17, 1.39) more likely also to be diagnosed with spinal pain, compared to undiagnosed counterparts of the same age and sex. Without bias corrections, we would have overestimated the magnitude of the association between major depression and spinal pain by a factor of approximately 2.0. CONCLUSION: Our results highlight a moderate and bi-directional association between two of the most prevalent disorders in military populations. Our results also highlight the importance of correcting for misclassification in electronic medical record data research.

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).