Nitrogen oxides were genetically linked to a sevenfold increased risk of systemic lupus erythematosus, according to a recent study. 

Investigators conducted a two-sample Mendelian randomization (MR) study to investigate causal relationships between air pollution and autoimmune diseases (ADs). The study, published in Scientific Reports, utilized genome-wide association study (GWAS) data from the UK Biobank (air pollutants) and the FinnGen cohort (autoimmune diseases) to explore the potential genetic links between five common air pollutants (PM2.5, PM2.5 to 10, PM10, nitrogen dioxide, and nitrogen oxides) and nine ADs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), ulcerative colitis (UC), and psoriasis.

Using single nucleotide polymorphisms as instrumental variables, the investigators employed the random-effects inverse variance weighted method as the primary analytical approach. The analysis revealed significant positive associations between nitrogen oxides and the risk of RA (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.01–2.14, P = .043), SS (OR = 2.29, 95% CI = 1.08–4.89, P = .032), and SLE (OR = 7.26, 95% CI = 2.25–23.40, P < .001). Additionally, PM2.5 exposure was associated with an increased risk of UC (OR = 1.68, 95% CI = 1.05–2.68, P = .032), and PM10 exposure was linked to psoriasis (OR = 1.34, 95% CI = 1.02–1.76, P = .037). Conversely, PM2.5 to 10 exposure appeared protective against SS (OR = 0.29, 95% CI = 0.10–0.90, P = .032).

To further explore mechanisms, a two-step MR analysis evaluated the mediating roles of common risk factors, including body mass index (BMI) and smoking. The study found that BMI mediated 6% (95% CI = 1%–10%) and smoking mediated 9% (95% CI = 2%–17%) of the effect of nitrogen oxides on RA. No mediating effects were observed for other ADs, indicating that much of the impact of air pollution on these conditions remains unexplained.

This study's use of a Mendelian randomization design provided preliminary insights into the causal relationship between air pollutants and autoimmune diseases but did not clarify the specific mechanisms involved, requiring further research. Additionally, limitations such as potential horizontal pleiotropy, a restricted sample size for air pollution GWAS data, and the focus on a European population highlight the need for larger, more diverse studies to validate these findings.

Sensitivity analyses, including leave-one-out testing and funnel plots, confirmed the stability of the findings, with no evidence of heterogeneity or horizontal pleiotropy. The investigators concluded that their findings demonstrated a causal relationship between air pollution and specific ADs. The study leveraged large-scale genetic data sets to explore the impact of environmental factors on autoimmune pathogenesis.

Full disclosures can be found in the published study.