| 1 | BMC Med. Genet. 2014 -1 15: 2 |
|---|---|
| PMID | 24387768 |
| Title | Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1. |
| Abstract | Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD). 在这里,我们描述一个comprehensive genome-wide study of bipolar disorder (BD), cross-referencing analysis from a family-based study of 229 small families with association analysis from over 950 cases and 950 ethnicity-matched controls from the UK and Canada. Further, loci identified in these analyses were supported by pathways identified through pathway analysis on the samples. Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as at SYNE1 on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and forschizophrenia. Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling. The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 and SYNE1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD,WDR60, SCN7A and SPAG16. |
| SCZ Keywords | schizophrenia |
| 2 | Mol Autism 2014 -1 5: 1 |
| PMID | 24410847 |
| Title | Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders. |
| Abstract | Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. 为了帮助阐明这种遗传复杂性，我们对来自40个具有远距离影响个体的40个家庭的100个ASD个体进行了整个外显子组测序。所有家庭都至少包含一对ASD堂兄。每个人都被敏捷的SURESELECT人类全部外显子试剂盒捕获，并在Illumina Hiseq 2000上进行了测序，并用Burrows-Wheeler Anigner（BWA），基因组分析工具基（GATK）（GATK）和SETTLESEQ进行了处理和注释。利用了有关每个家庭的基因分型信息，以确定下降相同的基因组区域（IBD）。然后评估通过IBD区域中发生并存在于每个家庭中所有受影响个体中的外显子组测序鉴定的变体，以确定哪些可能与疾病有关。优先考虑新颖且罕见的核苷酸改变（MAF，小于0.05），预计会通过改变氨基酸或剪接模式有害。 We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1),schizophrenia(WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the literature, we determined that variants occurred in ASD candidate genes 1.65 times more frequently than in random genes captured by exome sequencing (P?=?8.55 � 10-5). By studying these unique pedigrees, we have identified novel DNA variations related to ASD, demonstrated that exome sequencing in extended families is a powerful tool for ASD candidate gene discovery, and provided further evidence of an underlying genetic component to a wide range of neurodevelopmental and neuropsychiatric diseases. |
| SCZ Keywords | schizophrenia |