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

描述(由申请人提供)：Brinda K.Rana博士，加州大学圣地亚哥分校(UCSD)医学院精神病学系助理教授，正在与主要导师William Kreman博士和共同导师Nicholas Schork博士一起申请K01导师研究科学家发展奖。拟议的K01培训的目标是获得(1)认知老化研究；(2)研究设计；和(3)表观遗传学方面的培训。这次培训将使拉纳博士能够实现她的职业目标，即成为认知衰老基因组学领域的独立研究员。培训目标将通过实施拟议的研究、参与克莱曼博士实验室正在进行的认知评估、访问合作者Michael Lyons和Lindon Eaves进行双胞胎方法学培训以及参加斯坦老龄化研究所的研讨会、课程和研讨会来实现。拉纳博士的主要导师是克莱曼博士，他是加州大学圣迭戈分校的神经精神评估和老龄化研究专家，也是越南时代双胞胎老龄化研究(Vetsa)的主要调查员。拉纳博士的共同导师肖克博士是加利福尼亚州拉霍亚斯克里普斯研究所的一名统计遗传学家，他正在开发DNA甲基化方法。林登·伊夫斯博士、迈克尔·莱昂斯博士和迈克尔·尼尔博士是这个项目的合作者，他们将在孪生方法论方面指导拉纳博士。加州大学圣迭戈分校生物工程系的张昆博士是全基因组DNA甲基化技术方面的专家，将担任DNA甲基化研究的现场顾问。沙阿·戈尔山博士将担任将大量基因组数据建立数据库的顾问。这项名为《年龄相关认知下降的遗传和表观遗传因素--双胞胎研究》的研究的总体目标是通过表观遗传学研究更好地了解基因组和环境对年龄相关神经认知变化的预测作用。具体地说，来自Vetsa队列的DNA样本和纵向表型数据将用于实现这一目标。Vetsa是一项持续进行的纵向研究，旨在调查随着时间的推移对认知过程的遗传和环境贡献，具有特殊功能，包括对1200多个双胞胎进行双胞胎抽样，以估计表型的遗传力，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老化的预测因素。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老化中的作用。

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.