Predicting organismal phenotypes from genotype data is important for preventive and personalized medicine as well as plant and animal breeding. Although genome-wide association studies (GWAS) for complex traits have discovered a large number of trait- and disease-associated variants, phenotype prediction based on associated variants is usually in low accuracy even for a high-heritability trait because these variants can typically account for a limited fraction of total genetic variance. In comparison with GWAS, the whole-genome prediction (WGP) methods can increase prediction accuracy by making use of a huge number of variants simultaneously. Among various statistical methods for WGP, multiple-trait model and antedependence model show their respective advantages. To take advantage of both strategies within a unified framework, we proposed a novel multivariate antedependence-based method for joint prediction of multiple quantitative traits using a Bayesian algorithm via modeling a linear relationship of effect vector between each pair of adjacent markers. Through both simulation and real-data analyses, our studies demonstrated that the proposed antedependence-based multiple-trait WGP method is more accurate and robust than corresponding traditional counterparts (Bayes A and multi-trait Bayes A) under various scenarios. Our method can be readily extended to deal with missing phenotypes and resequence data with rare variants, offering a feasible way to jointly predict phenotypes for multiple complex traits in human genetic epidemiology as well as plant and livestock breeding.

Objective: Hepatitis C virus (HCV), being reported to be associated with a high prevalence of serological markers of autoimmunity in HCV-infected patients, and possibly sharing partial sequences in amino acid segments with thyroid tissue antigens, may be associated with interferon-a (IFN-a)-induced thyroid dysfunction in chronic hepatitis C patients. We conducted this study to clarify the issue. Design and Methods: One hundred and fifty chronic hepatitis C patients with normal baseline thyroid function were treated with IFN-a 2a, 2b and n1 (3-6 million Units three times weekly for 24 weeks). Pretreatment sera were tested for HCV genotype and HCV RNA levels. Serum thyrotropin, total thyroxine and free thyroxine index were performed every 4 weeks for 24 weeks followed by every 8 weeks for another 24 weeks. Results: Twenty-one (14.0%) patients developed early thyroid dysfunction (abnormal thyroid function during the first 3 months of therapy). Female gender, lower HCV RNA levels, IFN-a n1 and a lower IFN-a dose were significantly associated with early thyroid dysfunction. On multivariate analysis, gender, IFN-a preparation and HCV RNA levels were the significant factors associated with early thyroid dysfunction. Seven (4.7%) patients developed thyroid dysfunction during the second 3 months of IFN-a therapy. Taken together, 18.7% patients developed thyroid dysfunction. Female, mixed HCV genotype infection and lower HCV RNA levels were significantly associated with thyroid dysfunction. However, only gender remained significantly associated with IFN-a-induced thyroid dysfunction in multivariate analysis. Conclusions:The virologic features of HCV may be associated with thyroid dysfunction in chronic hepatitis C patients treated with IFN-a. Nevertheless, gender still plays the most important role in IFN-a-induced thyroid dysfunction.

Although the expression of extracellular matrix protein-1 (ECM1) has been documented in several tumor models, the function of ECM1 has remained unclear. In this study, expression of ECM1 was detected by real time PCR and immunohistochemistry. The role and mechanism of ECM1 overexpression in cholangiocarcinoma (CCA) cells were assessed by wound-healing, matrigel invasion assay and Western blotting. Expression of ECM1 was significantly elevated in CCA tissues than that in adjacent noncancerous, cholangitis and normal bile duct tissues. Its overexpression was associated with poor differentiation, lymph node metastasis, poor prognosis, and the level of CA199, MMP-9, estrogen receptor. Knockdown of ECM1 suppressed migration and invasion of CCA cells. Using PI3K or IKK inhibitor reduced the level of phospho-Akt or phospho-IκBα as well as ECM1. Taken together, overexpression of ECM1 may contribute to CCA initiation and progression through promoting migration and invasion of CCA cells, its overexpression was associated with Akt/NF-κB signaling axis.

Summary Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue. Method: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis. Result: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22–90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusion: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years.