Association of Intrapancreatic Fat Deposition with Mortality: A Prospective Cohort Study with Genetic Risk Profiling.

Area of Science:

• Medical research
• Genetics
• Epidemiology

Background:

• Pancreatitis and pancreatic cancer contribute to excess mortality.
• Excessive intrapancreatic fat deposition (IPFD) is implicated in exocrine pancreas diseases per the PANDORA hypothesis.
• The association between IPFD and mortality has not been previously studied.

Purpose of the Study:

• To investigate the relationship between IPFD and mortality.
• To explore the association of IPFD with all-cause and cause-specific mortality.

Main Methods:

• Analysis of UK Biobank participants (n=55,058) with IPFD quantified by MRI.
• Kaplan-Meier survival analysis and multivariable Cox-proportional hazard models.
• Genome-wide association study (GWAS) and Mendelian randomization, with a polygenic risk score (PRS) applied in an independent cohort (n=354,761).

Main Results:

• Excessive baseline IPFD was linked to increased all-cause mortality (HR=1.081) and vascular disease mortality (HR=1.247).
• GWAS identified 38 IPFD-associated SNPs; the derived PRS correlated with mortality outcomes.
• Consistent findings were observed in the MRI-naïve cohort using PRS as a genetic proxy for IPFD.

Conclusions:

• Excessive IPFD is associated with a higher risk of future mortality in the general population.
• The risk of mortality, particularly from vascular diseases, is elevated in individuals with excessive IPFD.