Genetic and Epigenetic Factors of Age-Related Cognitive Decline - A Twin Study

简介（由申请人提供）：Brinda K. Rana博士，加州大学圣地亚哥分校（UCSD）医学院精神病学助理教授，正在与主要导师William Kremen博士和联合导师Nicholas Schork博士一起申请K01指导研究科学家发展奖。提出的K01训练的目标是获得以下方面的训练：(1)认知衰老研究；(2)研究设计；(3)表观遗传学。这次培训将使Rana博士能够实现她的职业目标，成为认知衰老基因组学领域的独立研究人员。培训目标将通过以下几方面的结合来实现：进行拟议的研究，参加Kremen博士实验室正在进行的认知评估，与合作者Michael Lyons和Lindon Eaves一起访问双胞胎方法培训，以及参加Stein老龄研究所的讲习班、课程和研讨会。Rana博士的主要导师是Kremen博士，他是加州大学圣地亚哥分校神经精神评估和衰老研究方面的专家，也是越战时期双胞胎衰老研究（VETSA）的首席研究员。Rana博士的共同导师Schork博士是加州拉霍亚斯克里普斯研究所的统计遗传学家，他正在开发DNA甲基化方法。Drs。Lindon Eaves， Michael Lyons和Michael Neale是这个项目的合作者，他们将指导Rana博士使用双胞胎方法。加州大学圣地亚哥分校生物工程系张坤博士是全基因组DNA甲基化技术方面的专家，他将担任DNA甲基化研究的现场顾问。Shah Golshan博士将担任大量基因组数据数据库的顾问。拟议研究的总体目标是“与年龄相关的认知能力下降的遗传和表观遗传因素——一项双胞胎研究”，旨在通过表观遗传研究更好地了解与年龄相关的神经认知变化的基因组和环境预测因素。具体来说，来自VETSA队列的DNA样本和纵向表型数据将用于解决这一目标。VETSA是一项正在进行的纵向研究，专门用于调查随着时间的推移，认知过程的遗传和环境因素，其特殊功能包括对1200多对双胞胎的抽样，可以估计表型的遗传性，每个个体的详细认知和相关表型数据，生化表型如皮质醇水平，以及一些认知和生化表型的纵向数据。此外，表型数据从中年开始，这允许识别健康认知衰老的预测因子。将结合经典双胞胎设计、同卵双胞胎对照设计和非双胞胎设计来确定DNA甲基化在认知和大脑衰老中的作用。

DESCRIPTION (provided by applicant): Brinda K. Rana, PhD, an Assistant Professor in the Department of Psychiatry at the University of California, San Diego (UCSD) School of Medicine, is applying for the K01 Mentored Research Scientist Development Award with primary mentor Dr. William Kremen and co-mentor Dr. Nicholas Schork. The goals of the proposed K01 training are to obtain training in (1) cognitive aging research; (2) research design; and (3) epigenetics. This training will enable Dr. Rana to reach her career goal of an independent researcher in the field of genomics of cognitive aging. The training objectives will be met through a combination of conducting the proposed research, participating in on-going cognitive assessments in Dr. Kremen's laboratory, visits with collaborators Michael Lyons and Lindon Eaves for training in twin methodology, and participation in workshops, courses, and seminars at the Stein Institute for Research in Aging. Dr. Rana's primary mentor is Dr. Kremen, an expert in neuropsychiatric assessments and aging research at UCSD and Principle Investigator on the Vietnam Era Twin Study of Aging (VETSA). Dr. Rana's co-mentor, Dr. Schork, a statistical geneticist at The Scripps Research Institute in La Jolla, CA who is developing DNA methylation methodologies. Drs. Lindon Eaves, Michael Lyons, and Michael Neale are collaborators on this project and will mentor Dr. Rana in twin methodology. Dr. Kun Zhang in the UCSD Department of Bioengineering is an expert in whole genome DNA methylation technologies, and will serve as an on-site consultant for DNA methylation studies. Dr. Shah Golshan will serve as a consultant for databasing large amounts of genomic data. The overall goal of the proposed research, "Genetic and Epigenetic Factors of Age-Related Cognitive Decline-A Twin Study," is to better understand genomic and environmental predictors of age-related neurocognitive changes through epigenetic studies. Specifically, the DNA samples and longitudinal phenotype data from the VETSA cohort will be used to address this goal. VETSA is an ongoing longitudinal study specifically designed to investigate the genetic and environmental contributors to cognitive processes over time with special features that include twin sampling of over 1200 twins that enables the estimation of heritability of phenotypes, detailed cognitive and related phenotype data on each individual, biochemical phenotypes such as cortisol levels, and longitudinal data on some cognitive and biochemical phenotypes. In addition, the phenotype data starts at midlife which allows for the identification of predictors of healthy cognitive aging. A combination of classical twin design, co-twin control design, and non-twin design will be used to determine the role of DNA methylation in cognitive and brain aging.