Pancreatitis polygenic risk score is independently associated with all-cause acute pancreatitis risk in the UK Biobank.
acute pancreatitis
personalized medicine
polygenic risk score
triglycerides
Journal
Journal of gastroenterology and hepatology
ISSN: 1440-1746
Titre abrégé: J Gastroenterol Hepatol
Pays: Australia
ID NLM: 8607909
Informations de publication
Date de publication:
10 Oct 2024
10 Oct 2024
Historique:
revised:
09
08
2024
received:
18
04
2024
accepted:
24
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
10
10
2024
Statut:
aheadofprint
Résumé
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. 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. 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 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.
Sections du résumé
BACKGROUND AND AIM
OBJECTIVE
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.
METHODS
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.
RESULTS
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
CONCLUSIONS
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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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