RT Journal Article SR Electronic T1 Genetic determinants of chromatin accessibility and gene regulation in T cell activation across human individuals JF bioRxiv FD Cold Spring Harbor Laboratory SP 090241 DO 10.1101/090241 A1 Christine S. Cheng A1 Rachel E. Gate A1 Aviva P. Aiden A1 Atsede Siba A1 Marcin Tabaka A1 Dmytro Lituiev A1 Ido Machol A1 Meena Subramaniam A1 Muhammad Shamim A1 Kendrick L. Hougen A1 Ivo Wortman A1 Su-Chen Huang A1 Neva C. Durand A1 Ting Feng A1 Philip L. De Jager A1 Howard Y. Chang A1 Erez Lieberman Aiden A1 Christophe Benoist A1 Michael A. Beer A1 Chun J. Ye A1 Aviv Regev YR 2016 UL http://biorxiv.org/content/early/2016/12/02/090241.abstract AB The vast majority of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. Here, we analyzed Assay for Transposase-Accessible Chromatin (ATAC-seq) profiles from activated primary CD4+ T cells of 105 healthy donors to identify ATAC-QTLs: genetic variants that affect chromatin accessibility. We found that ATAC-QTLs are widespread, disrupt binding sites for transcription factors known to be important for CD4+ T cell differentiation and activation, overlap and mediate expression QTLs from the same cells and are enriched for SNPs associated with autoimmune diseases. We also identified numerous pairs of ATAC-peaks with highly correlated chromatin accessibility. When we characterize 3D chromosome organization in primary CD4+ T cells by in situ-Hi-C, we found that correlated peaks tend to reside in the same chromatin contact domains, span super-enhancers, and are more impacted by ATAC-QTLs than single peaks. Thus, variability in chromatin accessibility in primary CD4+ T cells is heritable, is determined by genetic variation in a manner affected by the 3D organization of the genome, and mediates genetic effects on gene expression. Our results provide insights into how genetic variants modulate chromatin state and gene expression in primary immune cells that play a key role in many human diseases.