Inflamm Bowel Dis. 2024 Dec 19:izae269. doi: 10.1093/ibd/izae269. Online ahead of print.

Greg Gibson ¹, John D Rioux ², Judy H Cho ³, Talin Haritunians ⁴, Akshaya Thoutam ¹, Maria T Abreu ⁵, Steven R Brant ⁶, Subra Kugathasan ⁷, Jacob L McCauley ⁵, Mark Silverberg ⁸, Dermot McGovern ⁴

Author information

¹School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.

²Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.

³Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

⁴Widjaja Foundation IBD Research Institute, Cedars Sinai Health Center, Los Angeles, CA, USA.

⁵Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.

⁶Robert Wood Johnson School of Medicine, Rutgers University, Piscataway, NJ, USA.

⁷Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

⁸Lunenfeld-Tanenbaum Research Institute IBD, University of Toronto, Toronto, ON, Canada.

Abstract

The past 2 decades have witnessed extraordinary advances in our understanding of the genetic factors influencing inflammatory bowel disease (IBD), providing a foundation for the approaching era of genomic medicine. On behalf of the NIDDK IBD Genetics Consortium, we herein survey 11 grand challenges for the field as it embarks on the next 2 decades of research utilizing integrative genomic and systems biology approaches. These involve elucidation of the genetic architecture of IBD (how it compares across populations, the role of rare variants, and prospects of polygenic risk scores), in-depth cellular and molecular characterization (fine-mapping causal variants, cellular contributions to pathology, molecular pathways, interactions with environmental exposures, and advanced organoid models), and applications in personalized medicine (unmet medical needs, working toward molecular nosology, and precision therapeutics). We review recent advances in each of the 11 areas and pose challenges for the genetics and genomics communities of IBD researchers.