Identification of lupus causal variants at 8p23.1 by mapping 3D genome

Majority of systemic lupus erythematosus (SLE)-associated single nucleotide polymorphisms (SNPs) are located in regions of genome that encode regulatory instructions for where and when gene products are produced in cells of human body. The SLE-associated SNPs identified in human genetic studies are correlated proxies for SLE-causal genetic variants that may be located tens of thousands of base pairs away on a chromosome. The identification of precise genomic locations of SLE-causal variants remains a critical challenge. Human genome is folded to form a dynamic 3-dimensional structure inside cell nucleus and the regulatory regions are thought to interact with genes via DNA looping mechanism. The 8p23.1 region on human chromosome 8 contains many SLE-associated genetic loci. We will map the 3-dimensional structure of 8p23.1 region to identify precise locations of lupus-causal genetic variants. The SLE-causal variants and their long-distance physical interactions with genes both inside and outside of the 8p23.1 region identified in the course of this project will result in a novel candidate list of SLE-susceptibility genes and will shed new light on gene-regulatory mechanisms involved in the SLE etiology.