LAUSR

Motivation: Twin studies estimate 50% of type 1 diabetes (T1D) risk is genetic. Genetic association has implicated T cells as central to the disease process. Thus, we generated chromatin accessibility profiles from CD4+ T cells isolated from 135 T1D cases and 144 controls and investigated whether (1) there are patterns of chromatin accessibility that differ from T1D patients compared to healthy controls; (2) established T1D risk variants influence chromatin accessibility. Methods: Frozen PBMCs were provided by the Type 1 Diabetes Genetics Consortium (T1DGC). CD4+ T cells were isolated using bead purification and Assay for Transposase Accessible Chromatin (ATAC-seq) was performed. ATAC-seq samples were processed using the PEPATAC pipeline and R packages edgeR and limm. Results: We tested for differences in accessibility between individuals with and without T1D adjusting for sex, age, and experimental variability. We identified 516 chromatin regions peaks with differential accessibility by T1D status (2 with increased and 514 with decreased accessibility at FDR Conclusion: These results provide hypotheses about molecular mechanisms of T1D in CD4+ T cells. Disclosure C.C. Robertson: None. W. Chen: None. S. Onengut-Gumuscu: None. P.J. Concannon: Stock/Shareholder; Self; Amgen. Other Relationship; Self; 10x Genomics. S.S. Rich: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK111906)