Approved Research

Gravity Sensors and Linear Acceleration Comparing Human and Mice Genomics

Lay summary

The incidence of dizziness increases from 22% for adults between 65 and 69 years of age to over 40% for adults between the ages of 80 and 84 years. Associated risks related to dizziness in the elderly include increased falls, depression, social isolation, fear, and overall functional decline. Balance impairment in the United States is reported to be 75.3% over the age of 70 years, and falls are sixth leading cause of death, with a 20% mortality rate in this age-group.               

Twin studies have found that this imbalance is 27% to 46% inheritable. Many disorders are polygenic, i.e. made up of a large number of genes with small effects; adult-onset diabetes is a polygenic syndrome, for example. We feel that the genetic component of imbalance may likewise be composed of multiple genes, given that many parts of the brain as well as inner ear organs are involved, including semi-circular canals, saccule, utricle, cerebellum, and higher brain centers that coordinate input from the eyes, ears, and proprioception  (the perception of the position and movement of the body) to keep us upright and mobile.

To study the balance system, we will study both animals and humans. The human analysis will consist of genome-wide association study in the UK Biobank based on self-report of falls and fractures secondary to these falls. The animal model is a group of about 100 different types of aging mice that have a genetic architecture that has been studied both in balance and in other disorders, such as hearing loss. We will perform a study of balance in mice using an objective vestibular test of their balance system. In addition, we will study their RNA, or expression of their genes in the relevant organ systems, i.e., the inner ear, to discover where in the balance system these relevant genes are expressed. Since this type of analysis is not possible in humans (we cannot biopsy the inner ear), we can not only identify genes and pathways that may be relevant to humans' age-related imbalance, but also identify where in the brain, inner ear, or body this occurs.

We anticipate that this study will take about three years, including analysis and comparison with other human populations. It will provide direction towards further research into diagnosis and treatment of this pervasive syndrome.

Scope extension: Exploratory Aim: Replicate a study of balance involving a specific balance disorder, i.e., Meniere's Disease, then perform whole exome sequencing on the cohort of Meniere's Disease from the UK Biobank