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The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P=5.07 × 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide.
Pubmed ID: 21423239
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THIS RESOURCE IS NO LONGER IN SERVICE, documented August 22, 2016. A multi-country collaboration among scientists and funding agencies to develop a public resource where genetic similarities and differences in human beings are identified and catalogued. Using this information, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors. All of the information generated by the Project will be released into the public domain. Their goal is to compare the genetic sequences of different individuals to identify chromosomal regions where genetic variants are shared. Public and private organizations in six countries are participating in the International HapMap Project. Data generated by the Project can be downloaded with minimal constraints. HapMap project related data, software, and documentation include: bulk data on genotypes, frequencies, LD data, phasing data, allocated SNPs, recombination rates and hotspots, SNP assays, Perlegen amplicons, raw data, inferred genotypes, and mitochondrial and chrY haplogroups; Generic Genome Browser software; protocols and information on assay design, genotyping and other protocols used in the project; and documentation of samples/individuals and the XML format used in the project.
View all literature mentionsSoftware package for analysis of large-scale genetic data sets with hundreds of thousands of markers genotyped on thousands of samples. BEAGLE can * phase genotype data (i.e. infer haplotypes) for unrelated individuals, parent-offspring pairs, and parent-offspring trios. * infer sporadic missing genotype data. * impute ungenotyped markers that have been genotyped in a reference panel. * perform single marker and haplotypic association analysis. * detect genetic regions that are homozygous-by-descent in an individual or identical-by-descent in pairs of individuals. Beagle can also be used in conjunction with PRESTO, a program for fast and flexible permutation testing. PRESTO can compute empirical distributions of order statistics, analyze stratified data, and determine significance levels for one-stage and two-stage genetic association studies. BEAGLE is written in Java and runs on any computing platform with a Java version 1.6 interpreter (e.g. Windows, Unix, Linux, Solaris, Mac).
View all literature mentionsThe Stanley Online Genomics Database uses samples from the Stanley Medical Research Institute (SMRI) Brain Bank. These samples were processed and run on gene expression arrays by a variety of researchers in collaboration with the SMRI. These researchers have performed analyses on their respective studies using a range of analytic approaches. All of the genomic data have been aggregated in this online database, and a consistent set of analyses have been applied to each study. Additionally, a comprehensive set of cross-study analyses have been performed. A thorough collection of gene expression summaries are provided, inclusive of patient demographics, disease subclasses, regulated biological pathways, and functional classifications. Raw data is also available to download. The database is derived from two sets of brain samples, the Stanley Array collection and the Stanley Consortium collection. The Stanley Array collection contains 105 patients, and the Stanley Consortium collection contains 60 patients. Multiple genomic studies have been conducted using these brain samples. From these studies, twelve were selected for inclusion in the database on the basis of number of patients studied, genomic platform used, and data quality. The Consortium collection studies have fewer patients but more diversity in brain regions and array platforms, while the Array collection studies are more homogenous. There are tradeoffs, the Consortium results will be more variable, but findings may be more broadly representative. The collections contain brain samples from subjects in four main groups: Bipolar Schizophrenia, Depression, and Controls Brain regions used in the studies include: Broadman Area 6, Broadman Area 8/9, Broadman Area 10, Broadman Area 46, Cerebellum The 12 studies encompass a range of microarray platforms: Affymetrix HG-U95Av2, Affymetrix HG-U133A, Affymetrix HG-U133 2.0+, Codelink Human 20K, Agilent Human I, Custom cDNA Publications based on any of the clinical or genomic data should credit the Stanley Medical Research Institute, as well as any individual SMRI collaborators whose data is being used. Publications which make use of analytic results/methods in the database should additionally cite Dr. Michael Elashoff. Registration is required to access the data.
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