Vitamin D level and risk of systemic lupus erythematosus and rheumatoid arthritis: a Mendelian randomization

The aim of this study was to examine whether the vitamin D level is causally associated with risk of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). We performed two-sample Mendelian randomization (MR) analyses using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods on publicly available summary statistics datasets using two vitamin D level genome-wide association studies (GWASs) as exposure and SLE and RA GWASs on people of European descent as outcomes. We selected three independent single-nucleotide polymorphisms located at SSTR4 (rs2207173), GC (rs2282679), and NADSYN1 (3829251) with genome-wide significance from two GWASs on vitamin D levels as instrumental variables. The IVW, weighted median, and MR-Egger regression methods yielded no evidence of a causal association between vitamin D level and risk of SLE (beta = 0.032, SE = 0.119, p = 0.789; beta = 0.233, SE = 0.274, p = 0.552; beta = 0.054, SE = 0.125, p = 0.665; respectively) or RA (beta = 0.026, SE = 0.061, p = 0.664; beta = 0.025, SE = 0.065, p = 0.695; beta = 0.025, SE = 0.065, p = 0.695; respectively). In addition, MR-Egger regression revealed directional pleiotropy was unlikely to be biasing the result for SLE (intercept = − 0.058, p = 0.545) or RA (intercept = − 0.027, p = 0.558). The MR estimates from IVW, weighted median, and MR-Egger regression analyses were consistent. MR analysis did not support a causal association between the vitamin D level and SLE or RA.