| Title: | Pancreatitis polygenic risk score is independently associated with all-cause acute pancreatitis risk in the UK Biobank |
| Journal: | Journal of Gastroenterology and Hepatology |
| Published: | 10 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39385584/ |
| DOI: | https://doi.org/10.1111/jgh.16759 |
Publication 13251
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Abstract
BACKGROUND AND AIM: Acute pancreatitis (AP) is a complex disease most commonly caused by gallstones, alcohol intake, or hypertriglyceridemia. Even in subjects with hypertriglyceridemia, the risk of AP is heterogeneous. Identifying individuals with a high genetic susceptibility to AP could contribute to a better risk stratification in the clinic. This study aimed to determine if a weighted polygenic risk score (PRS) of common variants in pancreatitis susceptibility genes can independently predict all-cause AP incidence in the general population.</p>
METHODS: A weighted PRS was calculated for 484 932 individuals from the UK Biobank, including 3346 individuals who developed AP during follow-up. The PRS included eight single nucleotide polymorphisms in known pancreatitis susceptibility genes.</p>
RESULTS: Individuals with a pancreatitis PRS above the 90th percentile had a 1.21-fold (1.03-1.43; P = 0.02) increased risk of AP compared with those with a pancreatitis PRS below the 90th percentile. When comparing individuals in the third tertile versus the first tertile, the risk of AP was 1.13-fold (1.00-1.28; P = 0.06) higher. Individuals with both a high triglyceride (TG) level and a high pancreatitis PRS (third tertile) had a 2.31-fold (1.83-2.93; P = 3.4 × 10-12) increased risk of AP compared with those with a low pancreatitis PRS and a low TG level (first tertile). Overall, the association between pancreatitis PRS and incident AP was independent of baseline TG level.</p>
CONCLUSIONS: Results of this study suggest that the accumulation of common variants in pancreatitis susceptibility genes is associated with all-cause AP incidence. Pancreatitis PRS could help clinicians identify patients who may be at higher risk of AP and who may benefit from more aggressive treatment.</p>
6 Authors
- Simon-Pierre Guay
- Eloi Gagnon
- Martine Paquette
- Sébastien Thériault
- Benoit J Arsenault
- Alexis Baass
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