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Exploration of a genomic expression and pathway analysis approach to neurocognitive performance: preliminary findings
Chad A Bousman1, Gursharan Chana2, Stephen J Glatt3, Sharon D Chandler1, Todd May1, James Lohr1, Ian P Everall2, William S Kremen1, Ming T Tsuang1
1Psychiatry, University of California, San Diego, CA, USA; 2Psychiatry, University of Melbourne, Melbourne, Victoria, Australia; 3Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
Abstract: Identification of genomic biomarkers for neurocognitive performance could revolutionize screening, diagnosis, staging, and/or prognosis practices for HIV-associated neurocognitive disorders (HAND). This study sought to explore the relationship between blood-based gene expression and neurocognitive performance. 8 healthy adults were recruited. Subjects were non-smokers, reported taking no medications, and were free of any psychiatric disorders. Correlations adjusting for education and ancestry were conducted to generate lists of genes significantly correlated with scores on neurocognitive test from the National Institute of Mental Health’s Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery (MCCB). Ingenuity pathway analysis was used to identify canonical pathways. For each of the 10 MCCB tests, large effect sizes (r > 0.49) were observed. 65% of the genes and 80% of canonical pathways were unique to 1 of the 10 MCCB tests, albeit none survived a 10% FDR correction. Minimal gene overlap was observed across tests; however, several overlapping canonical pathways were observed. Analysis of the relationship between gene expression alterations and neurocognitive performance may provide the potential for improving our ability to identify genomic markers of HAND as well as provide guidance to physicians and researchers in HIV medicine and other disciplines in their pursuit of viable genomic biomarkers for neurocognitive impairment.
Keywords: gene expression, cognitive, methodology, MATRICS
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