Gene Expression in Family with Diverse Psychopathology




Professor Of Genetics

Project Summary

Previous research has established that psychiatric disorders, like schizophrenia and bipolar disorder, have a complicated genetic architecture. However, recent findings have shown that it is not just specific genes controlling these traits, but also how much these genes are being transcribed. Through the Penn Undergraduate Research mentorship program, I had the opportunity to work under Dr. Laura Almasy to study gene expression in a family with an unusually high incidence of psychiatric disorders.

My major roles in this project involved using statistical and computational methods to determine the best method of classifying the disorders in this family and to analyze the transcription levels associated with this disorder. Based on the fourteen diagnoses assigned to members of the family by psychiatrists, individuals were characterized as having “psychosis disorders” or “mood disorders.” However, calculations indicated that neither of these broad categories had high heritabilities. Subsequent analysis of RNA expression data obtained from blood also did not show any significant difference in the mean expression of genes between the affected individuals and the controls. Further categorization of the disorders into more specific categories produced similar results. 

Because of this, all of those in the family affected by a psychiatric disorder were viewed as one group. While the calculated heritability was still moderate and there were no significant transcription levels, several of the genes with the lowest p values were found to play roles in immune function and have been previously linked to psychiatric disorders. Pathway analysis also showed significant enrichment of genes involved in leukocyte proliferation among the transcripts most associated with diagnosis. Considering many individuals in this family experienced their first episodes of psychosis after a high fever, this disorder could have an immunological component. These findings are consistent with other studies that show an immune basis for psychiatric disorders. Future research will focus on examining compromised immune function in this family.

Through this project I have learned to use the Linux command line, R, and more advanced Excel functions to organize and analyze large datasets. With this acquired knowledge, I was then able to use R for data visualization and the command line program Solar Eclipse for statistical computations. Presenting at lab meetings enabled me to develop the skills needed to share this data, which will prove to be an invaluable skill in my future in research. If anything, working on this project has been extremely fulfilling and II look forward to working on it in the school year.