Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease affecting multiple organs in the body. SLE affects mainly women of reproductive age; these individuals have a higher morbidity and mortality compared to the general population. SLE pathogenesis arises from an interplay between environmental and genetic factors; however, only a modest proportion of these factors have been identified, and the exact disease mechanisms remain incompletely understood. SLE can affect children and adolescents, although less frequently than in adults; however, pediatric SLE can be more severe and with a greater genetic component. For instance, a subset of pediatric-onset SLE has a monogenic cause. There is a knowledge gap regarding pediatric SLE compared with adult SLE; therefore, this study aims to help close this gap by studying the genetics of families of affected children. Identifying differences and similarities in genetic factors across age subgroups of SLE will help elucidate pathogenic mechanisms and inform diagnosis and treatment. Based on GWAS, hundreds of loci are associated with SLE risk, but each has a very small effect, and together they account for less than a third of the genetic variability of this rare and very heterogeneous disease. Most GWAS in SLE focus on adult-onset onset and do not account for the high heterogeneity of SLE. Implementing long-read whole-genome sequencing in families of affected minors can reveal rare or complex disease-related variants, as well as methylation patterns that influence disease mechanisms. This project aims to help close the knowledge gap regarding the genetic background of pediatric-onset SLE by sequencing well-characterised minors with SLE and their biological parents. So far, we have whole-genome long-read sequenced: - Eight families of children with SLE - One family of a child affected by another rheumatic disease - Two pairs of parent-offspring, both affected by the disease. We have used the Revio system from PacBio in collaboration with Clinical Genomics Stockholm. We need the Bianca project to proceed with analysing the families' methylomes, performing de novo target assembly of candidate complex genomic regions and predicting the potential effects of candidate variants. This approach can be extended to other autoimmune rheumatic diseases affecting children and adolescents.