Adiponectin and the risk of gastrointestinal cancers in East Asians: Mendelian randomization analysis

Abstract

Background Adiponectin is an important adipocytokine and has been associated with the risks of gastrointestinal cancers (GICs). Mendelian randomization (MR) analysis is needed to assess the causal relationships between adiponectin and GICs. Methods We retrieved the summary data of genome‐wide association studies for adiponectin and six types of GICs in East Asians. A series of quality control steps were performed to select the eligible genetic instrumental tools. Horizontal pleiotropy and between‐SNP heterogeneity were tested to choose the primary MR method. We also conducted sensitivity analyses to test the robustness of the main findings. Results We detected neither heterogeneity nor horizontal pleiotropy for the eligible SNPs in all of the MR analyses. Inverse variance weighted (IVW) was therefore used as the primary method, and suggested that per 10% increase in log‐transformed adiponectin level was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.88, 95% CI 0.81, 0.96), whereas with an increased risk of hepatocellular carcinoma (OR = 1.26, 95% CI 1.09, 1.44) and of biliary tract cancer (OR = 1.54, 95% CI 1.12, 2.12). However, only the association between adiponectin and HCC risk was statistically significant after correction for multiple testing. No statistically significant association was detected between adiponectin and esophageal (OR = 1.05, 95% CI 0.89, 1.23), pancreatic (OR = 1.04, 95% CI 0.78, 1.37), and colorectal cancers (OR = 1.00, 95% CI 0.93, 1.07). Sensitivity analyses did not find contradictory results. Conclusion High level of adiponectin may have a causal effect on and can serve as a biomarker for the carcinogenesis of gastric cancer, hepatocellular carcinoma, and biliary tract cancer.

The Impact of Different Intensities of Physical Activity on Serum Urate and Gout: A Mendelian Randomization Study

“…Moreover, none of the methods employed for detecting pleiotropy, including the MR-Egger intercept test, MR-PRESSO global test, funnel plots, and Cochran Q heterogeneity test, demonstrated evidence of horizontal pleiotropy that could distort this result. The Rucker framework used in our sensitivity analysis and a MR strategy by others [ 41 ] also support this result returned by IVW. Notably, after removing an instrumental variable that could lead to controversial results, this association reached the significance level set in our study (OR = 0.555, p = 0.006), further emphasizing the protective effect of moderate-intensity physical activity against gout.…”

“…Moreover, all initially identified genetic variants were clumped using PLINK to ensure that our instruments came from an independent set of variants (settings: clump-r 2 = 0.001 and clump-kb = 10,000) [ 40 ]. Then, data harmonization was performed to either correct or directly exclude the effects of ambiguous single-nucleotide polymorphisms (SNPs) with inconsistent alleles and palindromic SNPs with ambiguous strands [ 41 ]. The F-statistic for each instrument was estimated using F = beta 2 /SE 2 [ 42 , 43 , 44 ].…”

“…After that, we used MR-PRESSO to address pleiotropy issues. MR-PRESSO is an IVW variant [ 39 , 41 ] that adjusts estimates based on detected pleiotropic instruments [ 51 ]. Finally, we performed a leave-one-out (LOO) analysis based on the IVW estimator to assess whether the results were altered by individual instrumental variables [ 57 , 67 ].…”

Exploring the impact of computer game playing on cognitive function, Alzheimer's disease risk, and brain-derived neurotrophic factor levels: Basic evidence from Mendelian randomization

“…Measures were taken to either correct or exclude these problematic variants to ensure the reliability of the genetic instruments used in the analysis. 22 In the next stage, the F -statistic for each instrument was computed using the formula F = beta2/SE2. 23 Specifically, instruments with an F -statistic of less than 10 were considered weak and thus were excluded from further analysis to avoid introducing bias and uncertainty into the results.…”

Can Intelligence Affect Alcohol-, Smoking-, and Physical Activity-Related Behaviors? A Mendelian Randomization Study

“…According to a strategy by Jiang et al ( 2022 ), we estimated the causal effects separately with two estimators according to the detected directional horizontal pleiotropy. The inverse-variance weighted (IVW), the most efficient estimator ( Burgess et al 2019 ) that can return unbiased estimates under no directional horizontal pleiotropy ( Bowden et al 2016b ), was employed if no significant directional pleiotropy was detected.…”