Multiple Sclerosis and Major Depressive Disorder Share Little Genetic Liability

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A team of researchers sought to investigate the bidirectional relationship between multiple sclerosis and major depressive disorder with Mendelian randomization.

No evidence from a Mendelian randomization analysis supported a genetic liability associated with multiple sclerosis (MS) susceptibility among patients with major depressive disorder (MDD). These findings were published in the Multiple Sclerosis Journal.

Study researchers sourced data from recent meta-analyses of MDD (total: n=807,553 individuals; cases: n=246,363) and MS (cases: n=47,429; control group participants: n=68,374), which pooled data from multiple sources. Physicians diagnosed MS and 2 of the 3 MDD cohorts used self-reported symptoms of depression.

The study researchers identified 102 significant MDD risk variants and 233 MS risk variants. They compared genetic risk variants and clinical characteristics between groups.

Individuals with a genetic liability for MDD had no increased risk for MS (per doubling odds: odds ratio [OR], 1.07; 95% CI, 0.90-1.28; P =.43). The 98 overlapping genetic risk variants had significant heterogeneity (P <.0001) but little evidence of pleiotropy (intercept, -0.003; P =.78).

The subset of individuals that had genetic predisposition toward increased body mass index (BMI) did have significant risk for MS (per standard deviation [SD] increase in BMI: OR, 1.34; 95% CI, 1.09-1.65; P =.005).

Individuals with a genetic liability for MS did not have increased risk for MDD (per doubling odds: OR, 1.00; 95% CI, 0.99-1.01; P =.51). Findings indicated significant heterogeneity (P <.0001) among the 178 overlapping loci without evidence of pleiotropy (intercept, 0.001; P =.19).

The subset of individuals who were prone to have increased BMI did have higher risk for MDD (per SD increase in BMI: OR, 1.08; 95% CI, 1.01-1.15; P =.02).

These findings may have been limited by the significant heterogeneity observed among the data and the use of self-reported depression.

The study authors concluded that they did not find evidence for shared genetic liability for MDD and MS. Both conditions, however, had significant associations with obesity, which may indicate that weight management may be an effective intervention among both patient populations.


Harroud A, Marrie RA, Fitzgerald KC, et al. Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis. Mult Scler. Published online February 16, 2021. doi:10.1177/1352458521993075