High depression genetic burden associated with MS disease activity

In a Canadian study, a higher depression genetic burden was associated with increased MS disease activity. The findings exclude reverse causality as a reason for worse outcomes in those with depression. Depression polygenic score (PGS) is a potential biomarker for risk stratification.

Depression is a common comorbidity in MS, which is associated with increased disease activity and disability. Dr Kaarina Kowalec (University of Manitoba, Canada) phrased the research question as follows: Is the cumulative genetic burden for depression associated with MS disease activity and disability worsening? To measure this genetic burden of depression, the researchers used the PGS, which reflects the number of inherited common genetic variants, weighted by their effect sizes. Using genetic variants, which do not change from birth, also means reverse causation as an explanation for any association between the PGS and outcomes can be excluded.

Dr Kolwalec and colleagues used a case-control study design, using samples from 3 cohorts from Canada (IMID study), USA (CombiRx trial), and Sweden (SMSReg) with extensive longitudinal phenotypes. They included 3,420 relapsing-onset MS cases of European genetic ancestry, with a median follow-up of 3–5 years.

“We found that a higher depression PSG was associated with relapse risk,” Dr Kowalec said. “Every 1-standard-deviation increase in the PSG was associated with a 23% increased hazard of relapse in the meta-analysis” (incidence rate ratio 1.23; 95% CI 1.01–1.50). In the US cohort, which was the only clinical trial cohort, a higher depression genetic burden was also significantly associated with relapse risk (HR 2.20; 95% CI 1.35–3.60) and confirmed Expanded Disability Status Scale (EDSS) worsening (HR 1.51; 95% CI 1.03–2.22).

1. Manouchehrinia A, et al. The association between depression polygenicity and disease activity and disability worsening in multiple sclerosis. Abstract O132, ECTRIMS 2024, 17–20 October 2024, Copenhagen, Denmark.

Medical writing support was provided by Michiel Tent
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Posted on 25 September 2024