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Purpose: Coffee intake and apolipoprotein B levels have been linked to gastric, colorectal, and esophageal cancers in numerous recent studies. However, whether these associations are all causal remains unestablished. This study aimed to assess the potential causal associations of apolipoprotein B and coffee intake with the risk of gastric, colorectal, and esophageal cancers using Mendelian randomization analysis. Methods: In this study, we utilized a two-sample Mendelian randomization analysis to access the causal effects of coffee intake and apolipoprotein B on gastric, colorectal, and esophageal cancers. The summary statistics of coffee intake (n = 428,860) and apolipoprotein B (n = 439,214) were obtained from the UK Biobank. In addition, the summary statistics of gastric cancer, colorectal cancer, and esophageal cancer were obtained from the FinnGen biobank (n = 218,792). Inverse variance weighted, MR–Egger, weighted median, and weighted mode were applied to examine the causal relationship between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers. MR–Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. Steiger filtering and bidirectional mendelian randomization analysis were performed to evaluate the possible reverse causality. Results: The result of the inverse variance weighted method indicated that apolipoprotein B levels were significantly associated with a higher risk of gastric cancer (OR = 1.392, 95% CI 1.027–1.889, P = 0.0333) and colorectal cancer (OR = 1.188, 95% CI 1.001–1.411, P = 0.0491). Furthermore, multivariable Mendelian randomization analysis also revealed a positive association between apolipoprotein B levels and colorectal cancer risk, but the effect of apolipoprotein B on gastric cancer risk disappeared after adjustment of coffee intake, body mass index or lipid-related traits. However, we did not discover any conclusive evidence linking coffee intake to gastric, colorectal, or esophageal cancers. Conclusions: This study suggested a causal association between genetically increased apolipoprotein B levels and higher risk of colorectal cancer. No causal relationship was observed between coffee intake and gastric, colorectal, or esophageal cancers. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) analysis was performed to explore the effect of psoriasis on lipid metabolism traits and myocardial infarction (MI) risk and to analyze the proportion of the mediatory effect of lipid metabolism traits. Publicly accessible summary-level data for psoriasis, lipid metabolism traits, and MI were provided by the genome-wide association studies (GWASs) of the FinnGen Biobank, UK Biobank, and CARDIoGRAMplusC4D, respectively. A two-sample MR was carried out to evaluate the association of psoriasis with lipid metabolism traits and MI. Furthermore, the current research focused on determining if the impact of psoriasis on MI is mediated by lipid metabolism traits. The outcomes of the random effect inverse-variance-weighted (IVW) technique indicated a substantial link between genetically predicted psoriasis and a higher risk of low-density lipoprotein (LDL) cholesterol (OR: 1.006, 95% CI: 1.005–1.007, p = 0.024), apolipoprotein B (OR: 1.018, 95% CI: 1.010–1.026, p = 0.015), lipoprotein A (OR: 1.006, 95% CI: 1.002–1.010, p = 0.039), and MI (OR: 1.066, 95% CI: 1.014–1.121, p = 0.012). The percentages of the mediatory effect of LDL cholesterol, apolipoprotein B, and lipoprotein A under psoriasis conditions on MI risk was 7.4%, 10.2%, and 4.1%, respectively. Psoriasis was causally linked to an elevated risk of lipid metabolism levels and MI. This study further demonstrated that LDL cholesterol, apolipoprotein B, and lipoprotein A mediated the effect of psoriasis on MI risk. And timely lipid-lowering treatment should be given to MI patients. [ABSTRACT FROM AUTHOR]

Background and purpose: We used two‐sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid‐modifying drugs on intracranial aneurysm (IA). Methods: Genetic variants for the effects of high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A1, low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein B, and triglycerides and targets for lipid‐modifying drugs were selected from the genome‐wide discovery analyses of the UK Biobank. Summary‐level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. Results: Univariate MR analyses showed that the HDL‐C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715–0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663–0.906, p = 0.001). The multivariate MR–inverse variance weighted analysis showed that the HDL‐C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434–0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347–0.913, p = 0.02), and the LDL‐C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191–0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160–0.883, p = 0.025). Using genetic proxies of known lipid‐modifying drugs, we found that the increased HDL‐C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747–0.973, p = 0.018), and the decreased LDL‐C with 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080–2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022–3.371, p = 0.042). Conclusions: Genetically determined HDL‐C and LDL‐C reduce the risk of IA and rIA. The effects of different lipid‐modifying drugs on IA need to be further investigated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits.Research Design and Methods: We identified carriers of PCSK9 pLoF variants in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid and lipoprotein traits, which served as a positive control. Association of PCSK9 pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits was then evaluated as a measure for adverse effects.Results: We identified 374 individuals carrying one of 41 unique PCSK9 pLoF variants. As expected, we found that PCSK9 pLoF carriers had significantly lower LDL cholesterol C levels (P = 7.4 × 10-55) and apolipoprotein B levels (P = 7.6 × 10-50) than did noncarriers. However, we found no significant associations between pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits (P > 0.05).Conclusions: Our results do not support adverse effects of PCSK9 pLoF variants on glycemic traits, hepatobiliary function, or neurocognitive traits. [ABSTRACT FROM AUTHOR]