Study participants were recruited from the Wolaita zone of southern Ethiopia from podoconiosis-affected families (DNA samples were collected from both parents and two affected siblings); unaffected persons were recruited to serve as controls. All participants were from the same broad geologic area covered by reddish-brown clay soils containing colloid-size particles derived from volcanic basalt rocks.13 The genomewide association study was conducted with the use of samples from one randomly selected affected sibling (of the two recruited) from each family and an unaffected, unrelated control for each case patient. The eligibility criteria for controls were the current absence of podoconiosis, the absence of a personal or family history of podoconiosis, age of at least 50 years (to minimize misclassification of potential case patients as controls), residence in the study area for at least 25 years, exposure to the same irritant clay soil as the case patients, and inconsistent use of shoes. Consequently, the controls were older than the case patients (average age, 62 years vs. 24 years). The family-based association test included the affected sibling who was not included in the genomewide association study as well as both parents from each family.