Human Clusterin ELISA Kit

Genome-wide Association studies (GWAS) and candidate gene studies have identified the association between BIN1 rs744373 variant and Alzheimer's disease (AD) in Caucasian populations. Recently, a number of studies investigated the association between BIN1 rs744373 and AD in Asian populations. However, both positive and negative results have been identified. We consider that the relatively small sample sizes may lead to the lower statistical power. Here, we selected 71,168 samples (22,395 AD cases and 48,773 controls) from 19 articles containing 38 studies and reinvestigated this association using meta-analysis method. We observed a significant genetic heterogeneity and identified a significant association between rs744373 polymorphism with AD in pooled populations (P = 5 x 10(-07), OR = 1.12, and 95% confidence interval (CI) 1.07-1.17). In subgroup analysis, we not only identified significant genetic heterogeneity in East Asian but also in Caucasian. The subgroup meta-analysis only revealed significant association between rs744373 polymorphism with AD in the Caucasian populations (P = 3.38 x 10(-08), OR = 1.16, 95% CI 1.10-1.22), but not in the East Asian populations (P = 0.393, OR = 1.057, and 95% CI 0.95-1.15). The regression analysis suggested no significant publication bias. In summary, this large-scale meta-analysis highlighted the significant association between rs744373 polymorphism and AD in Caucasian populations but not in the East Asian populations.

Nearly 95% of susceptibility SNPs identified by genome-wide association studies (GWASs) are located in non-coding regions, which causes a lot of difficulty in deciphering their biological functions on disease pathogenesis. Here, we aimed to conduct a comprehensive functional annotation for all the schizophrenia susceptibility loci obtained from GWASs. Considering varieties of epigenomic regulatory elements, we annotated all 22,688 acquired susceptibility SNPs according to their genomic positions to obtain functional SNPs. The comprehensive annotation indicated that these functional SNPs are broadly involved in diverse biological processes. Histone modification enrichment showed that H3K27ac, H3K36me3, H3K4me1, and H3K4me3 were related to the development of schizophrenia. Transcription factors (TFs) prediction, methylation quantitative trait loci (meQTL) analyses, expression quantitative trait loci (eQTL) analyses, and proteomic quantitative trait loci analyses (pQTL) identified 447 target protein-coding genes. Subsequently, differential expression analyses between schizophrenia cases and controls, nervous system phenotypes from mouse models, and protein-protein interaction with known schizophrenia-related pathways and genes were carried out with our target genes. We finaly prioritized 10 target genes for schizophrenia (CACNA1C, CLU, CSNK2B, GABBR1, GRIN2A, MAPK3, NOTCH4, SRR, TNF, and SYNGAP1). Our results may serve as an encyclopedia of schizophrenia susceptibility SNPs and offer holistic guides for post-GWAS functional experiments.