the Utility of Genome-Wide Association Studies in Hepatology

Abstract

Over the last 4 years, more than 450 genome-wide association studies (GWAS) have been successfully performed in a variety of human traits, of which approximately 2% relates to the field of hepatology. Whereas the many robust susceptibility gene findings have provided insight into fundamental physiological aspects of the phenotypes that have been studied, the widespread application has also revealed important limitations of the GWAS design. This review aims to systematically summarize both the strengths and the weaknesses of GWAS, as well as underscore important experiences made in model diseases outside the field of hepatology. By reviewing the GWAS performed in hepatology so far on this broader background, extensions and guidelines for the rational application of the study design in hepatology are proposed.

Biomarkers for disease progression of primary sclerosing cholangitis

“…[79][80][81][82] It is still unknown whether individual differences in PSC sub-phenotypes are driven by genetic background. The PSC Immunochip sub-phenotyping project, a study initiated by the International PSC study group (IPSCSG) is currently investigating, these possible associations between PSC risk loci and PSC sub-phenotype.…”

PNPLA3 gene in liver diseases

“…The proportion of phenotypic variation in a trait (e.g., height, liver diseases) that is due to underlying genetic variation is defined as the heritability [2]. Albeit limited in number compared to other pathologies, genome-wide association studies (GWAS) in the field of liver diseases have significantly contributed to the field by revealing unsuspected associations between genetic variations and various phenotypes, and have generated new pathophysiological hypotheses [4]. An excellent illustration was provided in 2009 in chronic hepatitis C (CHC).…”

Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back–Looking Forward to Next-Generation Innovation

“…The goal of GWASs is to identify DNA sequence variants that affect an individual's risk to a disease or response to drug treatment through detection of associations between allele or genotype frequencies and trait status. In contrast to CGASs, GWASs investigate the possible association of genetic variations throughout the entire human genome and therefore represent comprehensive and unbiased scan of the genome (Daly, 2012;Karlsen et al, 2010).…”