Local genetic variation of inflammatory bowel disease in Basque population and its effect in risk prediction

Sci Rep. 2022 Mar 1;12(1):3386. doi: 10.1038/s41598-022-07401-2.

Abstract

Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract. Although its aetiology remains unknown, environmental and genetic factors are involved in its development. Regarding genetics, more than 200 loci have been associated with IBD but the transferability of those signals to the Basque population living in Northern Spain, a population with distinctive genetic background, remains unknown. We have analysed 5,411,568 SNPs in 498 IBD cases and 935 controls from the Basque population. We found 33 suggestive loci (p < 5 × 10-6) in IBD and its subtypes, namely Crohn's Disease (CD) and Ulcerative Colitis (UC), detecting a genome-wide significant locus located in HLA region in patients with UC. Those loci contain previously associated genes with IBD (IL23R, JAK2 or HLA genes) and new genes that could be involved in its development (AGT, BZW2 or FSTL1). The overall genetic correlation between European populations and Basque population was high in IBD and CD, while in UC was lower. Finally, the use of genetic risk scores based on previous GWAS findings reached area under the curves > 0.68. In conclusion, we report on the genetic architecture of IBD in the Basque population, and explore the performance of European-descent genetic risk scores in this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colitis, Ulcerative* / epidemiology
  • Colitis, Ulcerative* / genetics
  • Crohn Disease* / epidemiology
  • Crohn Disease* / genetics
  • DNA-Binding Proteins / genetics
  • Follistatin-Related Proteins* / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Inflammatory Bowel Diseases* / epidemiology
  • Inflammatory Bowel Diseases* / genetics
  • Polymorphism, Single Nucleotide
  • Spain / epidemiology

Substances

  • BZW2 protein, human
  • DNA-Binding Proteins
  • Follistatin-Related Proteins
  • FSTL1 protein, human