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

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

Koldo Garcia-Etxebarria  1   2 , Olga Merino  3 , Adrián Gaite-Reguero  4 , Pedro M Rodrigues  5   6   7 , Amaia Herrarte  8 , Ane Etxart  8 , David Ellinghaus  9 , Horacio Alonso-Galan  8   10 , Andre Franke  9 , Urko M Marigorta  4   7 , Luis Bujanda  5   8 , Mauro D'Amato  11   7   12
Affiliations

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

Koldo Garcia-Etxebarria et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Genetic background of the Basque cohort analysed in the present study. (A) Relationship of the Basque cohort within 1000 genomes project European populations, according to Principal Component Analysis. (B) Principal Component Analysis of the Basque cohort, coloured by their ancestry according to Admixture analysis. Graphics were depicted using R language 4.0.5 (https://www.r-project.org) and ggplot2 3.3.5 (https://ggplot2.tidyverse.org).
Figure 2
Figure 2
Genetic regression of the results of the present study and their counterparts from IIBDGC, for IBD and its subtypes. Circle size and colour depict regression coefficients. Inside the circle the significance of the regression coefficient, ***p < 0.001, **p < 0.01, *p < 0.05; otherwise, not significant.
Figure 3
Figure 3
Polygenic risk score (PRS) analysis of IBD and its subtypes. T-test p, p-value of the T-test comparing the PRS scores of cases and controls. (A) PRS calculated for all Inflammatory Bowel Disease samples using the PRS derived in Khera et al.. (B) Optimal PRS calculated for all Inflammatory Bowel Disease samples using IIBDGC results as model. (C) Optimal PRS calculated only for Crohn’s Disease samples using IIBDGC results as model. (D) Optimal PRS calculated only for Ulcerative Colitis samples using IIBDGC results as model. (E) Optimal PRS calculated only for Ulcerative Colitis samples, excluding HLA region, using IIBDGC results as model.
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References

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