Identifying Genetic Influences on Chromatin Accessibility During Human Cortical Development
Developmental neuropsychiatric diseases such as schizophrenia and autism have debilitating consequences to individuals and skyrocketing costs of care, creating a great burden to patients, their families, and society. Though the causes of these diseases are not well understood, specific letters and locations in the genome that increase risk for illness have recently been identified. These genetic changes found more often in people with neuropsychiatric diseases are guideposts pointing us for the first time towards an understanding of the neurobiological genesis of these complex behavioral diseases. However, this process is difficult because these locations are often in regions of the genome where the encoded function is not well understood. Our goal in this proposal is to create a functional map and mechanism between poorly understood genetic variation and much better understood genes. I will identify genetic variants associated with changes in chromatin accessibility, an indicator of functionality in non-coding genomic regions, during human cortical development. I will integrate these associations with previously acquired data to determine how genetic variation influences chromatin accessibility, binding of gene regulatory elements, expression, and risk for illness. Mechanistic insight derived from this project may allow design of rational therapeutics for developmental neuropsychiatric disorders that have seen a dearth of treatment for the past 60 years.