title: The cumulative effects of known susceptibility variants to predict primary biliary cirrhosis risk.
abstract: 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.
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: R
authors.initials: R
authors.lastname: Tang
authors.affiliation: 1] State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China [2] Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Miao
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.affiliation: Division of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Feng
authors.affiliation: 1] Department of Biochemistry and Molecular Medicine, University of California at Davis, Davis, CA, USA [2] Division of Rheumatology, Department of Medicine, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Seldin
authors.affiliation: Clinical Immunology, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Invernizzi
authors.affiliation: Division of Rheumatology, Department of Medicine, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: W
authors.identifier: 0000000178836439
authors.initials: W
authors.lastname: Liao
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D015203:Reproducibility of Results