Depression in multiple sclerosis patients associated with risk variant near NEGR1

Abstract

BackgroundA substantial number of patients diagnosed with multiple sclerosis (MS) suffer from depression in addition to physical symptoms and disability. Recent evidence suggests a stronger relationship may exist between MS and depression than previously thought, in which a diagnosis of depression may be prodromic to the development of MS. MethodsA genome-wide association study (GWAS) was performed to identify genetic variants associated with the development of depression in a cohort of MS patients. The control group (n = 1180) was composed of MS patients with no diagnoses of depression as determined by ICD-9 and ICD-10 billing codes present in the electronic health record (EHR). Separate analyses were performed for three different case groups: 1) MS patients having a depression diagnosis at any time (n = 182), 2) MS patients having a depression diagnosis one year pre-MS diagnosis (n = 27), and 3) MS patients having a depression diagnosis one year post-MS diagnosis (n = 130). Logistic regression analyses were also performed to test for associations between the development of depression and an APOE tagging variant, as APOE was previously linked to depressive affect in MS. An additional logistic regression analysis tested for associations between depression in MS patients and SNPs associated with depression in the general population. Pathway enrichment analyses were also conducted to identify pathways that link the two diseases. ResultsGWAS identified no novel associations between variants and a diagnosis of depression relative to a diagnosis of MS. One variant, rs1432639, associated with depression in the general population, was significantly associated with the development of depression post-MS diagnosis. The APOE-related SNPs were not associated with depression in this study population. An IGF1 pathway approached statistical significance in patients diagnosed with depression prior to a diagnosis of MS. Conclusionrs1432639 and the IGF1 pathway provide evidence for a genetic link between MS and depression that warrants further research.