Deciphering Genetic Pleiotropy to Inform Precision Psychiatry
Research by Olivia Veatch, PhD, Junior Faculty, Kansas Institute for Precision Medicine COBRE
It is well established that genetic factors influence risk for many neurodevelopmental, neuropsychiatric and neurological conditions. Furthermore, genes recurrently implicated in clinically distinct brain disorders encode proteins with similar biological functions suggesting underlying molecular mechanisms with pleiotropic effects. Leveraging omics data to detect and functionally characterize genetic systems with pleiotropic effects could be particularly useful to informing more effective treatment options by providing knowledge of how convergent mechanisms influence risk for multiple disorders in the same individual.
In addition to sharing genetic risk factors, numerous disorders of the brain have prevalent comorbid sleep and circadian rhythm problems. Sleep plays an integral role in the success of a multitude of physiological and behavioral processes—including molecular, cellular and network mechanisms of neuronal plasticity. Poor quality and mistimed sleep are associated with cognitive impairment and increased behavioral and mental health issues. Sleep disruption may then be a modifiable risk factor that when effectively managed can improve symptom severity and long-term health outcomes in individuals with brain disorders. We hypothesize that pleiotropic effects influence expression of sleep problems in individuals living with disorders of the brain and that proteins encoded by associated genes are targets for treatment of sleep disruption.
The goals of this research are to integrate genomics, transcriptomics and proteomics data generated from post-mortem brain tissue donated by individuals who were diagnosed with schizophrenia. We will use these data to determine if pleiotropic genetic variants associate with expression changes in drug targets relevant for treating sleep problems. We will also functionally characterize genetic mechanisms connecting schizophrenia with sleep problems. The long-term goal of this work is to inform genomic-driven precision medical care for sleep problems in individuals living with schizophrenia.
Select Research Publications:
- Veatch OJ, Mazzotti DR, Schultz RT, Abel T, Michaelson JJ, Brodkin ES, Tunc B, Assouline SG, Nickl-Jockschat T, Malow BA, Sutcliffe JS, Pack AI. Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data. J Neurodev Disord. 2022 Jun 24;14(1):39. PMCID: PMC9233372
- Veatch OJ, Butler MG, Elsea SH, Malow BA, Sutcliffe JS, Moore JH. An Automated Functional Annotation Pipeline That Rapidly Prioritizes Clinically Relevant Genes for Autism Spectrum Disorder. Int J Mol Sci. 2020 Nov 27;21(23). PMCID: PMC7734579
- Veatch OJ, Keenan BT, Gehrman PR, Malow BA, Pack AI. Pleiotropic genetic effects influencing sleep and neurological disorders. Lancet Neurol. 2017 Feb;16(2):158-170. PMCID: PMC7014582
- Veatch OJ, Pendergast JS, Allen MJ, Leu RM, Johnson CH, Elsea SH, Malow BA. Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay. J Autism Dev Disord. 2015 Jan;45(1):100-10. PMCID: PMC4289108
- Veatch OJ, Sutcliffe JS, Warren ZE, Keenan BT, Potter MH, Malow BA. Shorter sleep duration is associated with social impairment and comorbidities in ASD. Autism Res. 2017 Jul;10(7):1221-1238. PMCID: PMC7923457
Olivia Veatch, Ph.D.
Assistant Professor, Department of Psychiatry and Behavioral Sciences
Junior Faculty, Kansas Institute for Precision Medicine COBRE