Starting the journey: Understanding the roles of complement proteins in liver diseases through mendelian randomization

• Published in: Clinical and molecular hepatology Vol. 30; no. 2; pp. 150 - 153
• Main Authors: Rezaee-Zavareh, Mohammad Saeid, Kim, Naomy, Yang, Ju Dong
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Association for the Study of the Liver 01-04-2024; The Korean Association for the Study of the Liver; 대한간학회
• Subjects: Abdomen; Alcohol; Cancer therapies; Cholangitis; complement system proteins; Conflicts of interest; drug repositioning; Genomes; Hepatitis; hepatocellular carcinoma; Hepatology; Humans; Liver cancer; Liver cirrhosis; Liver Diseases; mendelian randomization; Mendelian Randomization Analysis; Metabolism; Proteins; Roles; 내과학; Drug repositioning; Hepatocellular carcinoma; Liver diseases; Mendelian randomization; Complement system proteins
• ISSN: 2287-2728; 2287-285X; 2287-285X
• DOI: 10.3350/cmh.2024.0116

[...]Mendelian randomization (MR) serves as a method for causal inference using observational data and single nucleotide polymorphisms as instrumental variables to infer causal relationships. [19] in a recently published paper assessed the causal association between 28 circulating complement components and CLDs, including alcohol-related cirrhosis (ALC), MASLD, and three major autoimmune liver diseases, namely AIH, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and HCC, through two-sample MR. In this study, the authors found a significant association between genetically predicted complement component levels of C1q C chain (C1QC) with AIH, C8 gamma chain (C8G) and complement factor H-related protein 5 (CFHR5) with PSC, CFHR1, CFHR2, and C1QC with ALC, C8G with MASLD, and finally CFHR2, C7, and C15 with HCC using the inverse-variance weighted (IVW) method. [...]future studies should confirm the association using other available GWAS data from other ancestries to confirm the generalizability of the results in a wider population with different ethnic backgrounds. Abbreviations CLD, chronic liver diseases; AIH, autoimmune hepatitis; ALC, alcohol-related cirrhosis; ALD, alcohol-associated liver disease; PSC, primary sclerosing cholangitis; PBC, primary biliary cholangitis; HCC, hepatocellular carcinoma; MASLD, metabolic dysfunction-associated steatotic liver disease; CFHR, complement factor H-related protein; C8G, complement C8 gamma chain; GWAS, genome-wide association study; WM, weighted median; IVW, inverse-variance weighted; MR, mendelian randomization; OR, odds ratio; CI, confidence interval 1.