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Using GWAS summary statistics and linkage disequilibrium score regression (LDSR), the study assessed disease co-development with hepatitis C virus-negative (HCV-negative) HCC and estimated genetic correlations and heritability across 901 UK Biobank traits.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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identifies genetic correlations between hepatocellular carcinoma and clinically relevant traits  \nYounghun Han 1,2,3,4 | Vikram R. Shaw 1  | Jinyoung Byun 1,2,3,4  | Aaron P. Thrift 3,4  | Catherine Zhu 1 | Donghui Li 5 | Rikita I. Hatia 6 | Robin Kate Kelley 7 | Sean P. Cleary 8 | Anna S. Lok 9 | Paige M. Bracci 10 | Jennifer B. Permuth 11,12  | Roxana Bucur 13 | Jennifer Knox 13 |  \nJian-Min Yuan 14  | Amit G. Singal 15 | Prasun K. Jalal 16 | R. Mark Ghobrial 17 | Yuko Kono 18 | Dimpy P. Shah 19 | Mindie H. Nguyen 20  | Neehar D. Parikh 9 | Richard Kim 11  | Hui-Chen Wu 21 | Hashem El-Serag 3,4 | Ping Chang 3 | Yun Shin Chun 22 | Jian Gu 6  | Chad Huff 6 | Asif Rashid 23 | Lu-Yu Hwang 24 | Alison P. Klein 25 | Saira A. Khaderi 26 | Ahmed O. Kaseb 5  |  \nKathrine A. McGlynn 27  | Lewis R. Roberts 28 | Manal M. Hassan 6 | Christopher I. Amos 1,2,3,4  \nCorrespondence  \nChristopher I. Amos, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.  \nEmail: [ciamos@salud.unm.edu](ciamos@salud.unm.edu)  \nFunding information  \nNational Institutes of Health, Grant/Award Numbers: P01CA263025, P30ES030285, P50CA210964, R01CA186566, R01CA274528, X01HG007490; Cancer Prevention and Research Institute of Texas, Grant/Award Number: RP200537  \n[Correction added on 29 Oct-2025, after first online publication: copyright line was changed] .  \nAbstract  \nHepatocellular carcinoma (HCC) mortality is increasing globally, partly due to the growing prevalence of nonviral liver diseases. Genome-wide association studies (GWAS) have identified genetic variants associated with HCC development. Leveraging GWAS summary statistics and linkage disequilibrium score regression (LDSR), we investigated disease co-development with hepatitis C virus-negative (HCV-negative) HCC to provide unique insights into HCC etiology and prioritize relationships for further causal inquiry. We utilized the LDSR statistical framework to estimate the genetic correlation and heritability between HCV-negative HCC with 901 epidemiologic, behavioral, and clinical traits from the United Kingdom Biobank (UKBB) . First, we set the threshold for observed scale heritability of each trait at 0.02 to ensure reliable inferences with adequate study power. Next, we observed significant positive  \nAbbreviations: ALD, alcohol-associated liver disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; EHR, electronic health records; FDR, false discovery rate; GGT, gammaglutamyl transferase; GWAS, genome-wide association studies; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IBD, inflammatory bowel disease; LD, linkage disequilibrium; LDSR, linkage disequilibrium score regression; MAF, minor allele frequency; MASLD, metabolic dysfunction-associated steatotic liver disease; MR, Mendelian randomization; SES, socioeconomic status; SNP, single-nucleotide polymorphism; UKBB, United Kingdom Biobank.  \nYounghun Han, Vikram R. Shaw, and Christopher I. Amos contributed equally to this study.  \nFor affiliations refer to page 1201  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2025 The Author(s) . International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.  \ngenetic correlations between HCV-negative HCC and blood-based biomarkers of liver injury (ALT, GGT) and allostatic load (including glycated hemoglobin, blood pressure, and total albumin) . We also identified a positive genetic correlation between HCV-negative HCC and diseases associated with metabolic dysfunction-associated steatotic liver disease (MASLD), including diabetes, hy","cbCaiphyWWYLqpb0","https://ap.wps.com/l/cbCaiphyWWYLqpb0","pdf",5232281,11,"English","# Abstract\n# Keywords / Abbreviations\n# What's New?\n# Introduction","[{\"question\":\"What method was used to study genetic correlations in this research?\",\"answer\":\"The study used linkage disequilibrium score regression (LDSR) with genome-wide association study (GWAS) summary statistics to estimate genetic correlation and heritability.\"},{\"question\":\"Which population and traits were analyzed?\",\"answer\":\"The analysis used HCV-negative HCC and 901 epidemiologic, behavioral, and clinical traits derived from the UK Biobank.\"},{\"question\":\"What were the main findings regarding genetic correlations?\",\"answer\":\"The authors observed significant positive genetic correlations between HCV-negative HCC and blood-based biomarkers of liver injury and allostatic load, and also identified positive correlations with diseases linked to metabolic dysfunction-associated steatotic liver disease (MASLD), including diabetes and hypertension.\"}]","Linkage disequilibrium score regression identifies genetic correlations between hepatocellular carcinoma and clinically relevant traits | PDF",1790687028,28]