Dataset Information

Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases.

ABSTRACT: A number of disease-associated genetic markers for common liver diseases have been identified using genome-wide association studies (GWASs). The GWAS strategy is based on genome-wide single-nucleotide polymorphism typing technologies, which are now commercially available, accompanied by statistical methods to identify host genetic factors that are associated with target diseases or complex genetic traits. One of the most striking features of the GWAS strategy is the ability to identify unexpected disease-associated genetic markers across the entire human genome. Here, we describe the technological aspects of the GWAS strategy with examples from actual GWAS reports related to hepatitis research, including drug response for patients with chronic hepatitis C, susceptibility to primary biliary cirrhosis, and hepatitis-B-related hepatocellular carcinoma.

SUBMITTER: Nishida N

PROVIDER: S-EPMC4521269 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases.

Nishida Nao N Tokunaga Katsushi K Mizokami Masashi M

Journal of clinical and translational hepatology 20130915 1

A number of disease-associated genetic markers for common liver diseases have been identified using genome-wide association studies (GWASs). The GWAS strategy is based on genome-wide single-nucleotide polymorphism typing technologies, which are now commercially available, accompanied by statistical methods to identify host genetic factors that are associated with target diseases or complex genetic traits. One of the most striking features of the GWAS strategy is the ability to identify unexpecte ...[more]

PMID: 26357606

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Project description:Prion diseases are fatal neurodegenerative diseases of humans and animals caused by the misfolding and aggregation of prion protein (PrP). Mammalian prion diseases are under strong genetic control but few risk factors are known aside from the PrP gene locus (PRNP). No genome-wide association study (GWAS) has been done aside from a small sample of variant Creutzfeldt-Jakob disease (CJD). We conducted GWAS of sporadic CJD (sCJD), variant CJD (vCJD), iatrogenic CJD, inherited prion disease, kuru and resistance to kuru despite attendance at mortuary feasts. After quality control, we analysed 2000 samples and 6015 control individuals (provided by the Wellcome Trust Case Control Consortium and KORA-gen) for 491032-511862 SNPs in the European study. Association studies were done in each geographical and aetiological group followed by several combined analyses. The PRNP locus was highly associated with risk in all geographical and aetiological groups. This association was driven by the known coding variation at rs1799990 (PRNP codon 129). No non-PRNP loci achieved genome-wide significance in the meta-analysis of all human prion disease. SNPs at the ZBTB38-RASA2 locus were associated with CJD in the UK (rs295301, P = 3.13 × 10(-8); OR, 0.70) but these SNPs showed no replication evidence of association in German sCJD or in Papua New Guinea-based tests. A SNP in the CHN2 gene was associated with vCJD [P = 1.5 × 10(-7); odds ratio (OR), 2.36], but not in UK sCJD (P = 0.049; OR, 1.24), in German sCJD or in PNG groups. In the overall meta-analysis of CJD, 14 SNPs were associated (P < 10(-5); two at PRNP, three at ZBTB38-RASA2, nine at nine other independent non-PRNP loci), more than would be expected by chance. None of the loci recently identified as genome-wide significant in studies of other neurodegenerative diseases showed any clear evidence of association in prion diseases. Concerning common genetic variation, it is likely that the PRNP locus contains the only strong risk factors that act universally across human prion diseases. Our data are most consistent with several other risk loci of modest overall effects which will require further genetic association studies to provide definitive evidence.

Dataset Information

Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases.

Publications

Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases.

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