دورية أكاديمية
Genome-Wide Association Study for Alcohol-Related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1.
العنوان: | Genome-Wide Association Study for Alcohol-Related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1. |
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المؤلفون: | Innes, Hamish, Buch, Stephan, Hutchinson, Sharon, Guha, Indra Neil, Morling, Joanne R, Barnes, Eleanor, Irving, Will, Forrest, Ewan, Pedergnana, Vincent, Goldberg, David, Aspinall, Esther, Barclay, Stephan, Hayes, Peter C, Dillon, John, Nischalke, Hans Dieter, Lutz, Philipp, Spengler, Ulrich, Fischer, Janett, Berg, Thomas, Brosch, Mario, Eyer, Florian, Datz, Christian, Mueller, Sebastian, Peccerella, Teresa, Deltenre, Pierre, Marot, Astrid, Soyka, Michael, McQuillin, Andrew, Morgan, Marsha Y, Hampe, Jochen, Stickel, Felix |
المساهمون: | UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie |
المصدر: | Gastroenterology, Vol. 159, no. 4, p. 1276-1289.e7 (2020) |
بيانات النشر: | W.B. Saunders |
سنة النشر: | 2020 |
المجموعة: | DIAL@USL-B (Université Saint-Louis, Bruxelles) |
مصطلحات موضوعية: | Adult, Aged, Europe, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterogeneous-Nuclear Ribonucleoproteins, Humans, Liver Cirrhosis, Alcoholic, Male, Middle Aged, Mitochondrial Proteins, Nuclear Proteins, Oxidoreductases, Phenotype, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Transcription Factors, Biomarker, Hepatic Fibrogenesis, Prognostic Factor, SNP |
الوصف: | BACKGROUND AND AIMS: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom Biobank (UKB) to identify polymorphisms associated with risk of alcohol-related liver disease. METHODS: We performed a GWAS of 35,839 participants in the UKB with high intake of alcohol against markers of hepatic fibrosis (FIB-4, APRI, and Forns index scores) and hepatocellular injury (levels of aminotransferases). Loci identified in the discovery analysis were tested for their association with alcohol-related cirrhosis in 3 separate European cohorts (phase 1 validation cohort; n=2545). Variants associated with alcohol-related cirrhosis in the validation at a false discovery rate of less than 20% were then directly genotyped in 2 additional European validation cohorts (phase 2 validation, n=2068). RESULTS: In the GWAS of the discovery cohort, we identified 50 independent risk loci with genome-wide significance (P < 5 × 10-8). Nine of these loci were significantly associated with alcohol-related cirrhosis in the phase 1 validation cohort; 6 of these 9 loci were significantly associated with alcohol-related cirrhosis in phase 2 validation cohort, at a false discovery rate below 5%. The loci included variants in the mitochondrial amidoxime reducing component 1 gene (MARC1) and the heterogeneous nuclear ribonucleoprotein U like 1 gene (HNRNPUL1). After we adjusted for age, sex, body mass index, and type-2 diabetes in the phase 2 validation cohort, the minor A allele of MARC1:rs2642438 was associated with reduced risk of alcohol-related cirrhosis (adjusted odds ratio, 0.76; P=.0027); conversely, the minor C allele of HNRNPUL1:rs15052 was associated with an increased risk of alcohol-related cirrhosis (adjusted odds ratio, 1.30; P=.020). CONCLUSIONS: In a GWAS of samples from the UKB, we identified and validated (in 5 European cohorts) single-nucleotide polymorphisms that affect risk of alcohol-related cirrhosis in ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0016-5085 1528-0012 |
العلاقة: | boreal:253418; http://hdl.handle.net/2078.1/253418Test; info:pmid/32561361; urn:ISSN:0016-5085; urn:EISSN:1528-0012 |
DOI: | 10.1053/j.gastro.2020.06.014 |
الإتاحة: | https://doi.org/10.1053/j.gastro.2020.06.014Test http://hdl.handle.net/2078.1/253418Test |
حقوق: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.85A05B2F |
قاعدة البيانات: | BASE |
تدمد: | 00165085 15280012 |
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DOI: | 10.1053/j.gastro.2020.06.014 |