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Discovery and Characterization of Genetic Risk Loci in Sjogren's Syndrome

The Sjögren's Genetics Network (SGENE) is an international collaboration focused on identifying and understanding the genetic variations that influence Sjögren's pathology. Collectively, SGENE collaborators from 26 different sites (5 in the United States; 21 in foreign countries) have recruited a large cohort of geographically diverse participants of European ancestry. Participants underwent extensive medical assessment for Sjögren's Disease (formerly Sjögren's Syndrome) using internationally accepted American-European Consensus Group (AECG) classification criteria or the American College of Rheumatology/European League Against Rheumatism classification criteria. Recruitment, sample collection, and genotyping were performed at unique SGENE sites in compliance with local institutional review board approval.

High-density SNP genotyping data were collated by the Oklahoma Medical Research Foundation (OMRF) and used to perform a GWAS of Sjögren's of European ancestry. Data quality control, GWAS imputation using the Haplotype Reference Consortium, panel version 1.1, and dbGaP preparation/posting were also performed at the OMRF. To facilitate research focused on understanding the genetics of Sjögren's Disease, the Genomic Summary Results from this GWAS are being made available herein (n=3232 Sjögren's cases; n=8962 healthy controls). To achieve adequate case-to-control ratios for the GWAS analyses, population-based control GWAS data were obtained from dbGaP (phs000428; phs000196; phs000187; phs000672. In accordance with IRB approval, subject consents, and data sharing restrictions, we have made available the individual-level genotyping data for a subset of Sjögren's cases (n=1,244) that were genotyped at the OMRF.

Bulk RNA-sequencing was also performed using total RNA extracted from peripheral whole blood samples from a subset of Sjögren's cases classified by status of Ro autoantibody (Ro-positive n=27; Ro-negative n=23) and healthy controls (n=27). In accordance with IRB approval, subject consents, and data sharing restrictions, we have made available the individual-level transcriptomic sequences as a subset of this cohort.

SmartSeq2 manual single cell RNA-sequencing (scRNA-seq) data was also generated from a subset of Sjögren's cases classified by status of Ro autoantibody (Ro positive n=9, Ro negative n=12) and from individuals with non-Sjögren's sicca syndrome (n=11). In accordance with IRB approval, subject consents, and data sharing restrictions, we have made available the individual-level transcriptomic sequences from a subset of this cohort.