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// Peng Han 1 , Guiyou Liu 2 , Xin Lu 3 , Minmin Cao 4 , Youling Yan 3 , Jing Zou 5 , Xiaobo Li 6 , Guangyu Wang 7 1 Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150040, China 2 Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China 3 Department of Gastroenterology, The First Hospital of Harbin, Harbin, 150001, China 4 Department of Endocrinology, The First Hospital of Harbin, Harbin, 150001, China 5 Department of Hematology, The First Hospital of Harbin, Harbin, 150001, China 6 Department of Pathology, Harbin Medical University, Harbin, 150081, China 7 Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150040, China Correspondence to: Xiaobo Li, email: lixiaobo@ems.hrbmu.edu.cn Guangyu Wang, email: guangyuwang@ems.hrbmu.edu.cn Keywords: genome-wide association study, colorectal cancer, rs9929218, meta-analysis, eQTL Received: November 26, 2015 Accepted: May 08, 2016 Published: June 01, 2016 ABSTRACT Colorectal cancer (CRC) is the third most common cancer. Large-scale genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants in European ancestry including the CDH1 rs9929218. Following GWAS and candidate studies evaluated the association between the CDH1 rs9929218 polymorphism and CRC in European, Asian and American populations. However, these studies reported inconsistent associations. Evidence shows that rs9929218 may regulate different gene expressions in different human tissues. Here, we reevaluated this association using large-scale samples from 16 studies (n=131768) using a meta-analysis method. In heterogeneity test, we did not identify significant heterogeneity among these studies. Meta-analysis using fixed effect model showed significant association between rs9929218 and CRC ( P =6.16E-21, odds ratio (OR) =0.92, 95% confidence interval (CI) 0.91-0.94). In order to validate the effect of rs9929218 variant on CDH1 expression, we further performed a functional analysis using two large-scale expression datasets. We identified significant regulation relation between rs9929218 variant and the expression of CDH1, ZFP90, RP11-354M1.2 and MCOLN2 by both cis- effect and trans- effect. In summary, our analysis highlights significant association between rs9929218 polymorphism and CRC susceptibility.

// Jinsong Wei 1 , Ming Li 2 , Feng Gao 3 , Rong Zeng 1 , Guiyou Liu 4 , Keshen Li 5, 6 1 Department of Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 2 Departmentof Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China 3 Department of Trauma and Emergency Surgeon, The Second Affiliated Hospital, Harbin Medical University, Harbin, China 4 Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China 5 Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 6 Stroke Center, Neurology & Neurosurgery Division, The Clinical Medicine Research Institute & The First Affiliated Hospital, Jinan University, Guangzhou, China Correspondence to: Guiyou Liu, e-mail: liuguiyou1981@163.com Keshen Li, e-mail: keshenli2012@163.com Keywords: osteoporosis, bone mineral density, pathway analysis, genome-wide association studies Received: November 12, 2015 Accepted: March 29, 2016 Published: April 23, 2016 ABSTRACT Osteoporosis is a common human complex disease. It is mainly characterized by low bone mineral density (BMD) and low-trauma osteoporotic fractures (OF). Until now, a large proportion of heritability has yet to be explained. The existing large-scale genome-wide association studies (GWAS) provide strong support for the investigation of osteoporosis mechanisms using pathway analysis. Recent findings showed that different risk pathways may be involved in BMD in different tissues. Here, we conducted multiple pathway analyses of a large-scale lumbar spine BMD GWAS dataset (2,468,080 SNPs and 31,800 samples) using two published gene-based analysis software including ProxyGeneLD and the PLINK. Using BMD genes from ProxyGeneLD, we identified 51 significant KEGG pathways with adjusted P

Many studies have investigated the association between single nucleotide polymorphism (SNP) rs6983267 and the risk of prostate cancer. However, results of these studies are inconsistent. Therefore, we summarised available data and performed a meta-analysis to determine this association. Relevant articles were identified by searching the PubMed, Web of Science and Embase database. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects model. We used dominant model (GG + TG vs TT), recessive model (GG vs TG + TT) and additive model (GG +TT vs TG) to determine the association between the rs6983267 polymorphism and risk of prostate cancer. Summary, 9 studies involving 8726 participants were included in this meta-analysis. Overall, though no association was observed between the rs6983267 polymorphism and risk of prostate cancer, subgroup analysis according to ethnicity showed a significant association between the rs6983267 polymorphism and risk of prostate cancer among white European men [recessive model: GG vs TG + TT, OR=1.21, (95% CI: 1.03, 1.42), P=0.02]. Our results indicate that the GG genotype of the rs6983267 polymorphism will increase individual susceptibility to prostate cancer in white European men.

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

Alzheimer's disease (AD) is an acquired disorder of cognitive and behavioral impairment. It is considered to be caused by variety of factors, such as age, environment and genetic factors. In order to identify the genetic affect factors of AD, we carried out a bioinformatic approach which combined genome-wide haplotype-based association study with gene prioritization. The raw SNP genotypes data was downloaded from GEO database (GSE33528). It contains 615 AD patients and 560 controls of Caribbean Hispanic individuals. Firstly, we identified the linkage disequilibrium (LD) haplotype blocks and performed genome-wide haplotype association study to screen significant haplotypes that were associated with AD. Then we mapped these significant haplotypes to genes and obtained candidate genes set for AD. At last, we prioritized AD candidate genes based on their similarity with 36 known AD genes, so as to identify AD related genes. The results showed that 141 haplotypes on 134 LD blocks were significantly associated with AD (P