| 1 | Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2012 Jun 29: 255-9 |
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| PMID | 22678782 |
| Title | [Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia]. |
| Abstract | To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT). Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay. Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits. Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | PLoS ONE 2013 -1 8: e67776 |
| PMID | 23922650 |
| Title | Association study of 167 candidate genes for schizophrenia selected by a multi-domain evidence-based prioritization algorithm and neurodevelopmental hypothesis. |
| Abstract | Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n=3819) under linkage peaks in the Irish Study of High-Density schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted. |
| SCZ Keywords | schizophrenia |