Historical Silk Road Connectivity and the Geographic Distribution of Behçet’s Disease: A Cross-National Ecological Analysis
DOI:
https://doi.org/10.62051/xyk9gc56Keywords:
Behçet’s disease; Silk Road; Spatial epidemiology.Abstract
Behçet’s disease (BD) is a systemic inflammatory disorder with a distinct geographic distribution along the Silk Road. Although HLA-B51 is regarded as the strongest known genetic susceptibility factor, differences in BD prevalence among populations cannot be explained solely by genetics, and the influence of long-term historical connectivity remains unclear. To address this gap, we constructed a cross-national ecological dataset of 20 countries and developed a Silk Road Exposure Index (SREI) based on distance to the reconstructed Silk Road and territorial overlap with a 500-km corridor buffer. Layered ordinary least squares (OLS) regression models evaluated the association between SREI and BD prevalence, sequentially adjusting for HLA-B51 frequency, latitude, Human Development Index, and infectious burden. Robustness analyses included Cook’s distance, leave-one-out analyses, Negative Binomial regression, and Spearman correlation. In the minimally adjusted model, SREI was positively associated with log-transformed BD prevalence (β = 0.3703, P = 0.021; R² = 0.264), but the association weakened after full adjustment (β = 0.1880, P = 0.458). Leave-one-out analyses showed a consistently positive effect direction, while Spearman correlation remained significant (ρ = 0.568, P = 0.009). These findings provide a quantitative framework for evaluating the Silk Road hypothesis in BD epidemiology and suggest that historical connectivity may reflect long-term interactions among population movement, genetic susceptibility, and environmental influences rather than acting as an independent determinant.
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