Bridging the Gap Between Genes and Schizophrenia

26 August 2011. As the search for genetic variants related to schizophrenia and other psychiatric diseases continues, researchers have begun trying to piece together how exactly some of these variants contribute to disease. Two studies published in August in the Archives of General Psychiatry combine genotyping with brain imaging to discover associations between common variants and proposed intermediate or “endo-” phenotypes of brain structure and function. One study, led by Nicholas Schork at the University of California in San Diego, finds a single nucleotide polymorphism (SNP) on 15q12 that associates with cortical thickness and cognition in schizophrenia. The other study, led by Daniel Weinberger at the National Institute of Mental Health (NIMH) in Bethesda, Maryland, links an SNP in ZNF804A to functional coupling between dorsal lateral prefrontal cortex and other regions of the brain.

These imaging genetics studies spur deeper thinking about just what associations between genetic variants and a disease mean. Researchers have begun to bridge this gap by focusing on more apparently tractable aspects of a disease, be it a discrete behavioral phenotype such as prepulse inhibition, or something closer to the underlying biology, such as changes in brain structure—both of which appear to be altered in schizophrenia. Relating genetic variants to these intermediate phenotypes may help discover more disease-related genes, or identify neural circuits that contribute to the disease (Meyer-Lindenberg et al., 2006). Though both new studies use brain imaging measures as an intermediate phenotype, one study takes the gene discovery approach, and the other a neural mechanism approach….

By Michele Solis
Schizophrenia Research Forum

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