ABSTRACT Associations between various genetic variants and the risk of hepatocellular carcinoma (HCC) have been extensively explored but produced contradictory results. The aim of the present systematic meta‐analysis was to determine and validate genetic variants that are associated with HCC risk. Two‐step literature searches of PubMed, Embase, Web of Science, and Google Scholar databases and various meta‐analyses were performed, and a comprehensive field synopsis and epidemiological evidence were provided. A total of 20,081 publications were identified, of which 830 were deemed eligible for inclusion. Eventually, 36 variants in 27 genes were identified to be associated with HCC risk. Moreover, cumulative epidemiological evidence of an association was graded as moderate for nine variants in eight genes (ESR1 rs2234693, GRP78 rs430397, HLA‐DP rs3077, HLA‐DQ rs2856718, MnSOD rs4880, TNFα rs361525, HFE rs1800562 and rs1799945, and UGT1A7 High/Low) and strong for three variants in three genes (IL‐1B rs1143627, COL18A1 rs7499, and NQO1 rs1800566); HFE rs1800562 was deemed to have a false‐positive association. Thus, 11 variants in 11 genes were identified to be associated with HCC risk. This synopsis helps elucidate the mechanisms of carcinogenesis of HCC and provides insights into the early diagnosis and novel treatments of HCC by targeting those potential genes.
Yu-Jin Shi, Bin Huang, Xiaohong Liu et al.· MedComm· 0 citations
Anxiety disorders represent a major psychiatric burden, yet their molecular underpinnings remain poorly understood. While observational studies have linked circulating lipids and proteins to mental health, causal inference is hampered by confounding and reverse causation. Here, we leveraged two-sample Mendelian randomization (MR) to systematically evaluate the causal effects of 179 plasma lipid species and 4,907 plasma proteins on anxiety disorders, using two large-scale independent GWAS datasets for replication. Significant findings from the primary inverse variance weighted analysis were validated using Bayesian Weighted MR and MR Robust Adjusted Profile Score methods to mitigate potential pleiotropy. Sensitivity analyses and reverse MR assessed robustness and directionality. Mediation analyses further explored whether protein signatures mediate lipid-anxiety associations. We identified three lipids with robust causal effects, with sterol ester (27:1/20:5) consistently conferring a protective effect across both cohorts. Additionally, 31 proteins showed significant causal links to anxiety. Notably, the protective effect of sterol ester (27:1/20:5) was partially mediated by the upregulation of SERPINA4 and ICT1, both of which exhibited protective associations. Our findings provide genetic evidence for causal roles of the plasma lipidome and proteome in anxiety disorders, and unveil a specific lipid-protein-anxiety pathway that may offer novel biomarkers and therapeutic targets. These results underscore the value of integrating multi-omic MR to dissect psychiatric disease mechanisms.
Jiahui He, Zehan Zhang, Yanan Wang et al.· Behavioural Brain Research· 0 citations