Imaging epigenetics of Alzheimer's Disease

描述（由申请人提供）：本K 02提案的短期目标是：1）通过添加高通量全基因组表观遗传组分来扩大申请人的主动成像遗传R 01的范围; 2）积极寻求统计遗传学和表观遗传学领域的额外培训; 3）与著名的统计和成像遗传学专家建立新的合作关系并加强现有的合作关系。K 02奖的长期目标是支持申请人的科学事业，并进一步促进她成长为AD领域多产和非常成功的独立调查员。 申请人已制定了一项积极的研究计划，重点是AD的成像遗传生物标志物。她最近资助的R 01奖研究了认知正常和前驱AD受试者的前瞻性纵向队列中临床，成像和转录组疾病相关特征之间的关联。这项建议的科学目标是扩大实验范围，包括新获得的表观遗传数据。短期科学目标是将表观遗传学与亲本R 01的基因组、转录组、临床和成像数据相结合，以阐明表观遗传学对基因表达、脑萎缩、脑淀粉样变性和疾病风险的影响。R 01和K 02的长期科学目标是确定新的疾病相关途径和治疗靶点。为了确保拟议工作的成功，申请人将得到一组在高度相关的领域和方法方面具有专业知识的杰出合作者的支持。

DESCRIPTION (provided by applicant): The short term objectives of this K02 proposal are: 1) to expand the scope the applicant's active imaging genetic R01 by adding a high-throughput genome-wide epigenetic component; 2) to actively seek additional training in the areas of statistical genetics and epigenetics; and 3) to establish new and enhance existing collaborations with prominent statistical and imaging genetics experts. The long-term objective of the K02 award is to bolster the applicant's scientific career and to further facilitate her growth into a prolific and highly successful independent investigator in the AD field. The applicant has developed an active research program focused on the imaging genetic biomarkers of AD. Her recently funded R01 award studies the associations between clinical, imaging and transcriptomic disease-associated traits in a prospective longitudinal cohort of cognitively normal and prodromal AD subjects. The objective of the science integral to this proposal is to expand the scope of the experiments to include newly acquired epigenetic data. The short-term scientific goals are to integrate epigenetics with the genomic, transcriptomic, clinical and imaging data from the parent R01 in order to elucidate the epigenetic effects on gene expression, brain atrophy, brain amyloidosis and disease risk. The long-term scientific goals of the R01 and K02 are to identify novel disease-associated pathways and therapeutic targets. To ensure the success of the proposed work, the applicant will be supported by a diverse group of distinguished collaborators with expertise in highly relevant fields and methods.