The purpose of this review was to explore how vocal affect recognition deficits impact the psychosocial functioning of people with moderate to severe traumatic brain injury (TBI). A systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines was conducted, whereby six databases were searched, with additional hand searching of key journals also completed. The search identified 1847 records after duplicates were removed, and 1749 were excluded through title and abstract screening. After full text screening of 65 peer-reviewed articles published between January 1999 and August 2019, only five met inclusion criteria. The methodological quality of selected studies was assessed using the Mixed Methods Appraisal Tool (MMAT) Version 2018 with a fair level of agreement reached. A narrative synthesis of the results was completed, exploring vocal affect recognition and psychosocial functioning of people with moderate to severe TBI, including aspects of social cognition (i.e., empathy; Theory of Mind) and social behaviour. Results of the review were limited by a paucity of research in this area, a lack of high-level evidence, and wide variation in the outcome measures used. More rigorous study designs are required to establish more conclusive evidence regarding the degree and direction of the association between vocal affect recognition and aspects of psychosocial functioning. This review is registered with Prospero.

OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.