Hereditary Genetics: Current Research

Investigating the role of DNA methylation in schizophrenia using family trios

8^th World Congress on Epigenetics and Chromosome

August 17, 2021 | Webinar

Aysheh Alrfooh, Nancy C. Andreasen, Ted Abel, Thomas Wassink, Thomas Nickl-Jockschat, and Marie E. Gaine

Department of Pharmaceutical Sciences and Experimental Therapeutics (PSET), College of Pharmacy, University of Iowa, Iowa City, IA
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA
Iowa Neuroscience Institute, University of Iowa, Iowa City, IA
Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA

Scientific Tracks Abstracts: Hereditary Genet

Abstract:

Schizophrenia is a severe neuropsychiatric disorder with debilitating cognitive deficits and psychosis. It has a genetic component of non-Mendelian inheritance with an estimated heritability of 65-80%, emerging from a complex interplay of genetic and environmental factors. To investigate this link between genetic and environmental factors, we focused on the most common epigenetic modification, DNA methylation. We used genomic DNA from human participants within family pedigrees (one child with schizophrenia and two unaffected parents) in a total of 60 families. This approach allows the identification of disease-specific patterns, as patients and parents largely share environmental influences. The DNA samples were processed on the Infinium Methylation EPIC array and the analysis of the raw data was carried out using R programming. The methylation level of each CpG site was regressed against the sample group (schizophrenia vs control) adjusting for specific covariates (age, sex, smoking status, and race). Our study identified five differentially methylated CpG sites (two hypermethylated and three hypomethylated in schizophrenia subjects) (corrected p-value < 0.05) and one differentially methylated region located upstream of the Glutamate Metabotropic Receptor 2 (GRM2) gene. GRM2 is a G-protein coupled receptor for glutamate neurotransmitters, which plays a pivotal role in the regulation of dopaminergic neurotransmission, a key mechanism in schizophrenia. Studies showed that GRM2 gene expression is altered in different brain regions in individuals with schizophrenia. Our findings suggest that the DNA methylation is altered in the GRM2 gene in schizophrenia, thus providing a unique opportunity to develop novel biomarkers for schizophrenia.