Causal associations of iron status and back pain risk: A Mendelian randomization study

Abstract

BackgroundObservational studies have previously suggested a link between iron status makers and back pain. We conducted a two-sample Mendelian randomization (MR) study to determine the putative causal relationship between systemic iron status and back pain.Materials and methodsIn this MR study, a genome-wide association study (GWAS) involving 48,972 individuals was used to identify genetic instruments highly associated with systemic iron status. The outcome data (back pain) were derived from the Neale Lab consortium’s summary data from the UK Biobank (85,221 cases and 336,650 controls). With the inverse variance weighted (IVW) method as the main analysis, conservative analyses (selecting SNPs with concordant change of iron status biomarkers) and liberal analyses (selecting SNPs with genome-wide significant association with each iron status biomarker) were carried out. For sensitivity analyses, the MR-Egger, MR-Egger intercept, weighted median, weighted mode, and MR based on a Bayesian model averaging approaches were used. The Cochran’s Q-test was used to detect heterogeneity.ResultsBack pain was associated with genetically instrumented serum iron (OR = 1.01; 95% CI = 1.00–1.02, p = 0.01), ferritin (OR = 1.02; 95% CI = 1.00–1.04, p = 0.02), and transferrin saturation (OR = 1.01; 95% CI = 1.00–1.01, p = 0.01). Furthermore, there was no evidence of a link between transferrin and the risk of back pain (OR = 0.99, 95% CI = 0.98–1.00, p = 0.08). The sensitivity analyses and Cochran’s Q-test indicated that no pleiotropy or heterogeneity was detected (all p > 0.05).ConclusionWe provided potential genetic evidences for the causal associations of iron status with increased incidence of back pain. However, the evidences were weakened due to the low power. Further larger MR studies or RCTs are needed to investigate small effects.

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

“…Due to the fact that all the data utilized was already in the public domain, there is no additional approval required. A twosample MR was utilized to assess the causal association between CP and AIDs, including ALS, CeD, IBD, MS, RA, SLE, T1D, and psoriasis (23)(24)(25). Briefly, MCP and CWP served as the exposures, while eight subtypes of AIDs served as the outcomes.…”

“…Observational researches are susceptible to confounding factors such as demographics or environmental exposure. Mendelian randomization (MR) is an alternative method of determining the causal association between an exposure and a disease result by using genetic variations as environmental exposure proxies ( 25 ). Because genetic variations are thought to be assigned at random before birth, they are relatively independent of environmental influences and established well before illness onset, limiting residual confounding and reverse causation difficulties that restrict traditional observational researches ( 26 ).…”

Using Mendelian Randomization to Study the Role of Iron in Health and Disease

“…They did, however, find that iron levels were positively associated with the risk of OA in women, indicating a sex-specific difference [72]. Furthermore, back pain has also been seen to be associated with genetically instrumented high serum iron, ferritin, and transferrin saturation [73].…”

Big data, big consortia, and pain: UK Biobank, PAINSTORM, and DOLORisk

“…As the genetic variants inherited by an individual are randomly assigned at conception and not subject to modification, it allows genetic markers to be used as a “proxy” for the exposure of interest, thus eliminating the risk of confounding or reverse causation. These studies have been able to establish a causal effect of C-reactive protein, 65 insomnia 103 and iron blood serum status 117 with back pain, and diabetes with frozen shoulder. 53 Furthermore, a bidirectional relationship was found to exist between insomnia and CP 21 and between prescription opioid use and depression and anxiety disorders, 100 whereas multisite CP was found to be a causative for major depressive disorder 63 and far sightedness.…”