Table 3:

Summary of loci associated with inflammatory bowel disease that were significantly different between First Nations and white participants and the putative biological relevance of each locus

LocusRelative prevalence of risk variant in First Nations participantsPutative biological relevance
ATG16L1Lower

  • Encodes an autophagy scaffold protein important for clearance of intracellular bacteria

NOD2Lower*

  • Encodes cytoplasmic pattern-recognition receptor of peptidoglycan (via muramyl dipeptide)

  • Important for the recognition of intracellular bacteria

  • Interacts with ATG16L1 protein to activate autophagy

IRGMHigher

  • Encodes a product involved in autophagy and clearance of intracellular bacteria

IL12BHigher

  • Encodes interleukin-23 subunit shared by interleukin-12

IL23RHigher

  • Encodes a subunit of the heterodimeric interleukin-23 receptor

TNFSF15Higher

  • Encodes tumour necrosis family member TL1A, which drives mucosal inflammation and enhances Th1 and Th17 CD4+ function

MHC region (four SNPS)Some higher, some lower

  • Most polymorphic region of the genome

  • Encodes a number of products involved in antigen presentation (HLA) and co-stimulatory pathways (BTNL2)

ICOSLGHigher

  • Encodes inducible T-cell co-stimulator ligand

PTGER4Lower

  • Encodes receptor of inflammatory prostaglandin E2

MST1Lower

  • Encodes macrophage-stimulating protein 1, which is involved in macrophage chemotaxis and regulation of inflammation

ZNF365Lower

  • Encodes zinc finger protein 365

C11orf30Lower

  • Encodes EMSY protein, interacts with BRCA2; also associated with eczema

MUC19, LRRK2Higher

  • MUC19 encodes a mucin-family protein

  • LRRK2 encodes a product involved in autophagy

PTPN2Lower

  • Encodes T-cell protein tyrosine phosphatase, which has a role in the modulation of inflammatory response

  • Note: MHC = major histocompatibility complex, SNP = single nucleotide polymorphism.

  • ↵* Cumulative carriage of variants in a leucine-rich repeat region important in muramyl dipeptide recognition was lower in First Nations participants.