Sinicato NA, et al. - Researchers personally interviewed 392 consecutive systemic lupus erythematosus (SLE) patients regarding history of SLE across three generations (first-, second-, and third-degree relatives) in order to assess the familial occurrence of SLE in a large Brazilian cohort. According to age at disease-onset, they stratified patients into childhood (cSLE; n=112) or adult (aSLE; n=280). In this study, 2574 first-degree relatives, 5490 second-degree relatives and 6805 third-degree relatives were identified. Observations revealed a greater decline in SLE recurrence rate by generation in cSLE vs aSLE. This indicates a more polygenic and epistatic inheritance and that fewer risk factors characterize aSLE that are individually stronger. The findings thereby suggest that cSLE vs aSLE has a higher genetic load and that the genetic architecture of the disease differs based on age at onset.