Journal Article

The cumulative effects of known susceptibility variants to predict primary biliary cirrhosis risk

Gershwin, M E, Bian, Z, Seldin, M F, Miao, Q, Ma, W, Tang, R, Feng, X, Liao, W, Invernizzi, P, Ma, X, Chen, H

2015

Overview

Multiple genetic variants influence the risk for development of primary biliary cirrhosis (PBC). To explore the cumulative effects of known susceptibility loci on risk, we utilized a weighted genetic risk score (wGRS) to evaluate whether genetic information can predict susceptibility. The wGRS was created using 26 known susceptibility loci and investigated in 1840 UK PBC and 5164 controls. Our data indicate that the wGRS was significantly different between PBC and controls ( P =1.61E−142). Moreover, we assessed predictive performance of wGRS on disease status by calculating the area under the receiver operator characteristic curve. The area under curve for the purely genetic model was 0.72 and for gender plus genetic model was 0.82, with confidence limits substantially above random predictions. The risk of PBC using logistic regression was estimated after dividing individuals into quartiles. Individuals in the highest disclosed risk group demonstrated a substantially increased risk for PBC compared with the lowest risk group (odds ratio: 9.3, P =1.91E−084). Finally, we validated our findings in an analysis of an Italian PBC cohort. Our data suggested that the wGRS, utilizing genetic variants, was significantly associated with increased risk for PBC with consistent discriminant ability. Our study is a first step toward risk prediction for PBC.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/43 / 631/250/38 / Alleles / Analysis / Biliary cirrhosis / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Case-Control Studies / Cirrhosis / Development and progression / Diagnosis / Female / Gene Expression / Genetic aspects / Genetic diversity / Genetic Predisposition to Disease / Genetic research / Genetic susceptibility / Genetic Variation / Genome-wide association studies / Genomes / Health aspects / Homeopathy / Human Genetics / Humans / Immunology / Liver cirrhosis / Liver Cirrhosis, Biliary - genetics / Male / Materia medica and therapeutics / Methods / Odds Ratio / original-article / Polymorphism, Single Nucleotide / Primary biliary cirrhosis / Reproducibility of Results / ROC Curve / Therapeutics