Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequencing fidelity. Genome wide SNP density analysis identified 18 SNP hotspots with comparison to the 1000 Genome Projects (1KGP) data. A subset of the genes adjacent to SNP hotspots showed statistically significant enrichment in immunological processes. Genes adjacent to indel hotspots were functionally related to G-protein coupled signaling pathways. Further analyses elucidated significantly more JIA SNPs with regulatory potential compared to 1KGP data. Furthermore, SNPs located within linkage disequibilium (LD) blocks containing previously identified JIA-associated SNPs demonstrated higher regulation potential compared to SNPs outside LD blocks. We also demonstrated enrichment of novel JIA variants in histone modification peaks and DNase hypersensitivity sites in B cells. This study greatly expands the number of genetic variants that may contribute to JIA and give us some clues into what may trigger this disease. To date, this study is the first deep WGS effort on children with JIA and provides useful genetic resources for research communities particularly in understanding JIA etiology.