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BackgroundPodoconiosis is a non-infectious neglected tropical disease that causes progressive swelling of the lower limbs in an estimated 4 million people globally. Podoconiosis has been associated with prolonged exposure to certain soils, however no specific causative component has been identified. We conducted a systematic review of articles to investigate links between podoconiosis and mineral, geochemical and climate factors affecting soil genesis (pedogenesis).Methodology/principal findingsA systematic search was conducted across five electronic databases: Embase, Global Health, Medline, GeoRef and Web of Science. Searches were from database inception to January 2024. Primary quantitative research from any region was included, qualitative studies and those not in English were excluded. The AXIS tool was used to assess study quality and risk of bias. Twenty-seven studies were included and narrative synthesis was used to interpret data from tissue samples, soil samples, and remote sensed bedrock and pedogenic factors. Nine studies found a correlation between podoconiosis occurrence and regions with underlying alkalic volcanic bedrock, and six linked pedogenic factors (altitude and rainfall) with disease occurrence. Several studies linked specific soil mineralogy and geochemistry with endemic regions, including an abundance of phyllosilicate clay minerals, quartz, and trace elements, notably iron, beryllium and zirconium.ConclusionsThis systematic review is the first to be conducted on the literature linking pedogenic factors with podoconiosis globally. Study quality was low for some of the earlier (1970s) studies. Several soil mineralogical and geological variables were linked with podoconiosis prevalence, particularly kaolinite, smectite, micas, quartz, iron oxides and trace elements. However, it remains unclear whether these are covariates or direct contributors to the pathogenesis of the disease and what the role of other peculiarities of soils (complex mineral-organic or material-climate combined factors) might be. Studies on the enrichment of minerals and elements during pedogenesis should be prioritised in future research.Protocol registrationPROSPERO International prospective register of systematic reviews registration number CRD42024499266.