The relationship between digit ratio (2D:4D) and autoimmune diseases: A systematic review and meta-analysis

To explore the association between the second-to-fourth digit ratio (2D:4D) and autoimmune diseases (AIDs).

Relevant studies were retrieved from multiple databases up to October 2025. The 2D:4D ratio of both hands (2D:4D R + L), right hand minus left hand (ΔR - L 2D:4D), right hand (2D:4D R), left hand (2D:4D L), and Type 3 finger pattern (index finger shorter than the ring finger) were extracted. The pooled standardized mean difference (SMD) and odds ratio (OR) with their respective 95% confidence interval (95% CI) were calculated.

Among 4465 searched studies, 20 studies from 14 publications were finally included, involving 6958 patients, with included diseases encompassing osteoarthritis (n = 5966), multiple sclerosis (n = 308), systemic lupus erythematosus (n = 235), Hashimoto's thyroiditis (n = 168), Graves' disease (n = 33), rheumatoid arthritis (n = 205), and ankylosing spondylitis (n = 43). AID patients had a significantly lower overall 2D:4D ratio and higher prevalence of Type 3 finger patterns compared with healthy controls (SMD: -0.180, 95% CI: -0.350 to -0.010; OR: 1.645, 95% CI: 1.388 to 1.950). Subgroup analysis showed that overall 2D:4D ratios and heterogeneity were significantly decreased in the subgroups of osteoarthritis, radiograph-based measurement, and patients aged over 60 years. Moreover, female patients had a significantly higher 2D:4D ratio and a markedly lower proportion of Type 3 finger patterns compared with male patients.

Our study indicated that 2D:4D ratios were significantly decreased in patients with AIDs. The 2D:4D ratio could potentially be a promising non-invasive biomarker for AID susceptibility, providing a basis for the potential link between sex hormones and AIDs.