Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder that affects millions worldwide. Genome-wide association studies (GWAS) have identified 200 IBD-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 IBD loci using high-density genotyping in 67,852 individuals. Of the 139 independent associations identified in these regions, 18 were pinpointed to a single causal variant with >95% certainty, and an additional 27 associations to a single variant with >50% certainty. These 45 variants are significantly enriched for protein-coding changes (n=13), direct disruption of transcription factor binding sites (n=3) and tissue specific epigenetic marks (n=10), with the latter category showing enrichment in specific immune cells among associations stronger in CD and gut mucosa among associations stronger in UC. The results of this study suggest that high-resolution, fine-mapping in large samples can convert many GWAS discoveries into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

Inflammatory bowel disease (IBD) involves interaction between host genetic factors and environmental triggers. CCDC88B maps within one IBD risk locus on human chromosome 11q13. Here we show that CCDC88B protein increases in the colon during intestinal injury, concomitant with an influx of CCDC88B+lymphoid and myeloid cells. Loss of Ccdc88b protects against DSS-induced colitis, with fewer pathological lesions and reduced intestinal inflammation in Ccdc88b-deficient mice. In a T cell transfer model of colitis, Ccdc88b mutant CD4+ T cells do not induce colitis in immunocompromised hosts. Expression of human CCDC88B RNA and protein is higher in IBD patient colons than in control colon tissue. In human CD14+ myeloid cells, CCDC88B is regulated by cis-acting variants. In a cohort of patients with Crohn’s disease, CCDC88B expression correlates positively with disease risk. These findings suggest that CCDC88B has a critical function in colon inflammation and the pathogenesis of IBD.

Caregivers involved in child welfare report receiving fewer services than they anticipated or desired. To date, service needs and barriers research has focused on mental health care, though this pattern of unmet needs likely extends to other critically important areas (i.e., physical health, basic needs, school, social support). Further, there is lack of a standardized measure that captures these constructs. The current study developed a self-report measure of needs, use, and barriers across a wide range of service areas. Participants were caregivers of children involved in child abuse or neglect investigations (N = 32, 59% Latino, 50% alleged perpetrator) and were recruited as part of a larger study evaluating a multidisciplinary response to allegations in a metropolitan U.S. county. Items were generated based on existing needs assessments and consultation from researchers and caseworkers. The C-SNAB appeared to have adequate coverage of the breadth of services needed (33 items) and barriers faced (19) and had good predictive validity. About 93% of caregivers endorsed at least 1 unmet service need. Caregivers experienced an average of 4 unmet needs and 7 barriers to accessing services. The current study provides an approach to practically and comprehensively assessing service needs, use and barriers within this population.