Dietary factors are believed to potentially influence the risk of pancreatitis. Here, we systematically investigated the causal relationships between dietary habits and pancreatitis by using two-sample Mendelian randomization (MR). Large-scale genome-wide association study (GWAS) summary statistics for dietary habits were obtained from the UK Biobank. GWAS data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were from the FinnGen consortium. We performed univariable and multivariable MR analyses to evaluate the causal association between dietary habits and pancreatitis. Genetically driven alcohol drinking was associated with increased odds of AP, CP, AAP and ACP (all with p < 0.05). Genetic predisposition to higher dried fruit intake was associated with reduced risk of AP (OR = 0.280, p = 1.909 × 10⁻⁵) and CP (OR = 0.361, p = 0.009), while genetic predisposition to fresh fruit intake was associated with reduced risk of AP (OR = 0.448, p = 0.034) and ACP (OR = 0.262, p = 0.045). Genetically predicted higher consumption of pork (OR = 5.618, p = 0.022) or processed meat (OR = 2.771, p = 0.007) had a significant causal association with AP, and genetically predicted higher processed meat intake increased the risk of CP (OR = 2.463, p = 0.043). Our MR study showed that fruit intake may be protective against pancreatitis, whereas dietary intake of processed meat has potential adverse impacts. These findings may inform prevention strategies and interventions directed toward dietary habits and pancreatitis. Full article

Variation in vitamin B₁₂ levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B₁₂ status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B₁₂ levels, serving as genetic instruments for vitamin B₁₂ status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B₁₂ status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B₁₂ status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B₁₂ status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B₁₂ status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20–0.50) and pernicious anaemia (0.29, 0.19–0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B₁₂ status is potentially protective of risk of vitamin B₁₂ deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B₁₂ status in disease diagnosis, progression and management remains to be investigated. Full article

Over the last several decades, there has been a considerable growth in type 2 diabetes (T2DM) in Asians. A pathophysiological mechanism in Asian T2DM is closely linked to low insulin secretion, β-cell mass, and inability to compensate for insulin resistance. We hypothesized that genetic variants associated with lower β-cell mass and function and their combination with unhealthy lifestyle factors significantly raise T2DM risk among Asians. This hypothesis was explored with participants aged over 40. Participants were categorized into T2DM (case; n = 5383) and control (n = 53,318) groups. The genetic variants associated with a higher risk of T2DM were selected from a genome-wide association study in a city hospital-based cohort, and they were confirmed with a replicate study in Ansan/Ansung plus rural cohorts. The interacted genetic variants were identified with generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS)-nutrient interactions were examined. The 8-SNP model was positively associated with T2DM risk by about 10 times, exhibiting a higher association than the 20-SNP model, including all T2DM-linked SNPs with p < 5 × 10⁻⁶. The SNPs in the models were primarily involved in pancreatic β-cell growth and survival. The PRS of the 8-SNP model interacted with three lifestyle factors: energy intake based on the estimated energy requirement (EER), Western-style diet (WSD), and smoking status. Fasting serum glucose concentrations were much higher in the participants with High-PRS in rather low EER intake and high-WSD compared to the High-EER and Low-WSD, respectively. They were shown to be higher in the participants with High-PRS in smokers than in non-smokers. In conclusion, the genetic impact of T2DM risk was mainly involved with regulating pancreatic β-cell mass and function, and the PRS interacted with lifestyles. These results highlight the interaction between genetic impacts and lifestyles in precision nutrition. Full article