My research centers on the use of genetic and other multi-omic data to better understand the genomic mechanisms of disease risk in several related autoimmune conditions: Sjögren’s disease (SjD), systemic lupus erythematosus (lupus), neuromyelitis optica, and multiple sclerosis. Most of these diseases have had several large genome-wide association studies (GWAS), including 10,000-100,000 genotyped cases and surpassing 100 associated genetic regions. In contrast, the understanding of SjD genetic risk lags far behind. In 2022, we published the largest GWAS of SjD of European ancestry, which included 3700 genotyped cases and increased the total number of genome-wide significant SjD risk loci from 12 to 22 (Khatri, et al. Nat Commun. 2022); seven of the previously established loci were identified in our 2013 publication (Lessard, et al. Nat Genet. 2013). This work was made possible through the Sjögren’s Genetics Network (SGENE), a collaborative network of >25 global institutions that I lead. Our efforts to expand the SGENE and increase the ancestral diversity of our genotyped population are ongoing with the goal to perform a GWAS with 10,000 SjD cases, bridging the gap between the genetic understanding of SjD and other related autoimmune diseases.

Most of the genetic variants statistically associated with increased disease risk are positioned in noncoding regions of the genome and, if functional, alter the expression of specific genes through changes in the regulatory mechanisms that control transcription. In addition to performing the GWAS studies that identify regions of genetic association, my research aims to determine how specific genetic variants associated with Sjogren’s and lupus disrupt molecular mechanisms that contribute to disease risk. A significant amount of this work is supported by the Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) program, which I joined as an investigator in 2022. While my research has primarily focused on understanding the genetics of Sjögren’s and lupus, the impact of our work expands to other related autoimmune diseases. Uncovering the similarities and differences between the unique and common disease traits promises to improve our understanding of the genomic regulation that controls the human immune system in health and disease.