Analysis of Coding Variants Associated with Age-Related Phenotypes

与年龄相关表型相关的编码变异分析

基本信息

批准号：
8823714
负责人：
Laura M Raffield
金额：
$ 0.08万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2015-06-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8823714
关键词：
Adult Affect African American Aging Aging-Related Process Area Behavioral Blindness Blood Vessels Bone Density Brain Calcified Cardiovascular Diseases Cerebrovascular Disorders Characteristics Code Cohort Studies Comorbidity Complement 1q Complex Cytokine Receptors DNA Sequence Data Data Set Databases Development Diabetes Mellitus Discipline Disease Elderly Evaluation Family Family member Gene Family Genes Genetic Genetic Risk Genetic Variation Genotype Goals Health Heart Human Genetics Impaired cognition Individual Inflammation Inflammatory Interleukin-1 Interleukin-18 Interleukin-6 Investigation Knowledge Lead Life Style Link Magnetic Resonance Imaging Measures Meta-Analysis Metabolic Metabolism Methods Mind Mutation National Heart, Lung, and Blood Institute Non-Insulin-Dependent Diabetes Mellitus Pathogenesis Pathology Pathway interactions Patients Pharmacotherapy Phenotype Physical Function Plasma Play Process Proteins Research Research Personnel Risk Role Scientist Stroke Structure Surveys Technology Testing Training Programs Tumor Necrosis Factor-alpha United States Variant Vascular Diseases Vascular calcification adiponectin age related base bead chip cardiovascular disorder risk cognitive function cohort cytokine exome exome sequencing experience follow-up forest genetic variant high risk improved interest member mortality next generation sequencing pandemic disease personalized care personalized medicine receptor receptor binding tool trait

项目摘要

DESCRIPTION (provided by applicant): Many comorbidities of the aging process, including cardiovascular disease, cognitive decline, and metabolic dysregulation, are thought to be significantly influenced by genetic factors. Type 2 diabetes (T2D), a disease which affects more than 25% of adults over age 65 in the United States, is also thought to have a significant genetic component, and individuals with T2D are at high risk for age-related comorbidities. Common and uncommon coding genetic variants may play a significant role in these age-related comorbidities, and this project aims to elucidate coding variants which are significantly associated with a wide range of biomedical measures characteristic of aging and with mortality. Illumina(R) HumanExome BeadChips, which include over 240,000 coding variants, will allow rapid and comprehensive analysis of relevant coding variants in the Diabetes Heart Study cohort, an extensively phenotyped family-based cohort enriched for patients with T2D. Our initial focus will be on the C1q and tumor necrosis factor (TNF) superfamily of genes. Uncommon coding variants in a member of this family, adiponectin, which lead to a dramatic reduction in plasma levels of this protein have recently been discovered, and we hypothesize that coding variants in other C1q/TNF superfamily members, which have diverse roles in metabolism, inflammation, and other processes, may contribute to age-related phenotypes. Genes related to inflammation, such as cytokines and their receptors, will also be of particular interest, as inflammatory processes are key to the pathogenesis of many age-related diseases, including T2D. Interesting findings from the Exome Chip data from the Diabetes Heart Study will be replicated in other cohorts relevant to aging. The proposed research will further my development as an independent investigator and give me valuable experience in the meaningful application of human genetics tools to aging research.

描述（由申请人提供）：衰老过程的许多合并症，包括心血管疾病，认知能力下降和代谢失调，被认为受遗传因素的影响很大。 2型糖尿病（T2D）是一种影响美国65岁以上成年人的疾病，也被认为具有重要的遗传成分，而具有T2D的个体患有与年龄相关的合并症的风险很高。常见和不常见的编码遗传变异可能在这些与年龄相关的合并症中起重要作用，并且该项目旨在阐明与广泛的生物医学测量与衰老的特征和死亡率相关的广泛相关的编码变体。 Illumina（R）人类X型浆果包括超过240,000个编码变体，将允许对糖尿病心脏研究队列中相关的编码变体进行快速而全面的分析，这是一种广泛的表型基于家族的同类，对T2D患者富含。我们最初的重点是基因的C1Q和肿瘤坏死因子（TNF）超家族。最近已经发现了该家族成员脂联素的不常见编码变体脂联素，从而导致该蛋白质的血浆水平急剧降低，我们假设在其他C1Q/TNF超级家族中编码变体，它们在代谢症，代谢性，在代谢性，在代谢中具有多种作用，炎症和其他过程可能有助于与年龄相关的表型。与炎症有关的基因，例如细胞因子及其受体，也将特别感兴趣，因为炎症过程是包括T2D在内的许多年龄相关疾病的发病机理的关键。来自糖尿病心脏研究的外显子芯片数据中的有趣发现将在与衰老有关的其他同类中复制。拟议的研究将进一步发展作为独立研究者的发展，并为我提供了有意义的人类遗传学工具在衰老研究中的宝贵经验。