RESUMO
Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Proteínas do Tecido Nervoso/genética , Transtorno Obsessivo-Compulsivo/genética , Estudos de Casos e Controles , Lobo Frontal/metabolismo , Humanos , Pais , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Proteínas Associadas SAP90-PSD95 , População Branca/genéticaRESUMO
The type of systems covered here are not just speculative ideals but practical, working products installed in an ever increasing number of UK hospital establishments. Some sixty major hospitals have had systems supplied by my own company, very similar to those described, over the previous five year period. In addition, systems supplied by other competent companies show us that this trend is not just 'Technology for Technology's sake' but an important step forward in alarm management strategy.