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Genome-wide Investigation of the Interplay Between Age-Related Hearing Loss and Smoking Behaviors

年龄相关性听力损失与吸烟行为之间相互作用的全基因组调查

基本信息

批准号：
9813620
负责人：
RENATO POLIMANTI
金额：
$ 15.17万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9813620
关键词：
Affect Age Age-Years Aging Alleles Auditory Bayesian Network Biological Biological Process Biotechnology Blood Brain Brain imaging Brain region Characteristics Chromatin Chronic Disease Climacteric Complex Computer Simulation Dangerousness Data Data Reporting Data Set Diet Habits Disease Ear Elderly Environment Epidemiology Evaluation Follow-Up Studies Genes Genetic Genetic Variation Genetic study Goals Growth Factor Health Health Professional Hearing Hearing Tests Hearing problem Human Human Genetics Image Analysis Impairment Individual Investigation Labyrinth Lead Link Literature Magnetic Resonance Imaging Malignant Neoplasms Mediating Mediation Mental Depression Meta-Analysis Metabolic Pathway Metabolism Molecular National Health and Nutrition Examination Survey Nerve Neural Pathways Nicotine Noise Noise-Induced Hearing Loss Nucleic Acid Regulatory Sequences Nurses&apos Health Study Other Genetics Pathway interactions Patient Self-Report Pharmaceutical Preparations Phenotype Play Poison Population Presbycusis Prevention strategy Process Proxy Quality of life Quantitative Trait Loci Randomized Reproductive History Risk Risk Factors Role Sampling Smoker Smoking Smoking Behavior Smoking Status Social isolation Social status Specificity Structure Techniques Testing Therapeutic Tobacco Tobacco smoking behavior United States aged biobank chromosome conformation capture cigarette smoking cohort cytokine database of Genotypes and Phenotypes epidemiology study gene environment interaction genetic association genetic variant genome wide association study genome-wide genome-wide analysis hearing impairment hearing loss risk imaging genetics improved insight learning algorithm metabolomics middle ear neuroimaging nicotine exposure novel ototoxicity psychologic public health relevance response risk variant skills smoking cessation trait

项目摘要

ABSTRACT. Age-related hearing loss is a common disorder defined as the loss of the hearing with aging. In the United States, approximately 33% of the population between ages of 65 and 74 are subjected to hearing loss, and after 75 years of age, about 50% of the population have hearing problems. There are many causes of age-related hearing loss, including age-induced changes in the in the inner and middle ear and also complex changes along the nerve pathways from the ear to the brain. Epidemiological studies, such as The Epidemiology of Hearing Loss Study and National Health and Nutrition Examination Survey 1999-2004, have shown that the major risk factors for age-related hearing loss are noise exposure and smoking. Very limited information is available regarding the molecular pathways involved in age-related hearing loss and how smoking behaviors increase its risk. Our previous results suggest that genetic variation can play a role in moderating the effect of smoking on age-related hearing loss reducing smoking-induced damage in brain regions involved in auditory function. In the current proposal, we will apply genome-wide approaches to identify additional mechanisms involved in the age-related hearing loss induced by smoking behaviors. Specifically, we will conduct a genome-wide association study of age- related hearing loss in more than 500,000 subjects (>150,000 nicotine-exposed, >350,000 nicotine-unexposed). We will use the genetic and phenotypic information from cohorts from the UK Biobank, the Nurses' Health Studies I and II, the Health Professionals Follow-Up Study, and the National Center for Biotechnology Information the database of Genotypes and Phenotypes to conduct a genome-wide association study of hearing loss in individuals exposed to nicotine. A follow-up study will be performed with respect brain structure and activity using magnetic resonance imaging data from the UK Biobank. Additionally, we will conduct a multivariable Mendelian Randomization to investigate which metabolomic alterations and/or brain-structure changes mediate the causal relationship between smoking and hearing loss. The goal of this analysis is to verify the causal effect and the mediation processes involved in the interplay between smoking behaviors and hearing loss. The expected findings will provide novel insights regarding the molecular mechanisms by which smoking behaviors cause age-related hearing loss A better understanding of its genetics could permit us to develop more effective preventive strategies and therapeutic approaches that can improve the quality of life of the growing elderly population.

摘要。年龄相关性听力损失是一种常见的疾病，被定义为听力损失