RESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aß processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Imunidade/genética , Lipídeos/genética , Proteínas tau/genética , Idoso , Estudos de Casos e Controles , Feminino , Testes Genéticos/métodos , Estudo de Associação Genômica Ampla/métodos , Haplótipos/genética , Humanos , Metabolismo dos Lipídeos/genética , MasculinoRESUMO
BACKGROUND: In an effort to identify health and safety training needs for various groups of workers related to weapons of mass destruction, including chemical, biological, radiological, and nuclear weapons and high yield explosives (CBRNE), a conference, "Worker Training in a New Era: Responding to New Threats," was held at the Johns Hopkins Bloomberg School of Public Health in October 2002. METHODS: Two questions were addressed: Which general skills and knowledge are common to all workers who might be exposed to terrorist threats from CBRNE weapons? What are the particular skills and knowledge relevant to these threats that are specific to workers in different sectors? RESULTS: Thirteen core components for pre- and post-event training were identified. Pre-event training applies to all workers. Post-event training applies to selected personnel including first responders, skilled support personnel, and other workers involved in these operations. Recommendations to improve worker safety training related to preparedness include: identify specific competencies for worker pre- and post-event training; coordinate Federal policy on worker training for CBRNE hazards; adopt federal guidelines or standards on worker training for new CBRNE threats, based on the competencies and coordinated Federal policy; conduct an inventory of training programs and other resources that could be used or adapted for use for new threats; and develop new training content and methods for pre- and post-event training to address specific competencies. CONCLUSIONS: Given the possibility for the introduction of CBRNE threats into the workplace, all workers need some training in the potential hazards involved: the individual worker's specific role in an emergency; incident command; activation of the emergency notification system; use of personal protective equipment (PPE); and safe evacuation of the workplace. While some occupational sectors have developed effective training related to these new threats, there is a need to develop, implement, and evaluate training programs across many different sectors of the workforce.