School of Medicine Publications and Presentations
Document Type
Article
Publication Date
1-1-2015
Abstract
Background
Although case-control approaches are beginning to disentangle schizophrenia’s complex polygenic burden, other methods will likely be necessary to fully identify and characterize risk genes. Endophenotypes, traits genetically correlated with an illness, can help characterize the impact of risk genes by providing genetically relevant traits that are more tractable than the behavioral symptoms that classify mental illness. Here we present an analytic approach for discovering and empirically validating endophenotypes in extended pedigrees with very few affected individuals. Our approach indexes each family member’s risk as a function of shared genetic kinship with an affected individual, often referred to as the coefficient of relatedness. To demonstrate the utility of this approach, we search for neurocognitive and neuroanatomic endophenotypes for schizophrenia in large unselected multigenerational pedigrees.
Methods
A fixed effect test within the variance component framework was performed on neurocognitive and cortical surface area traits in 1,606 Mexican-American individuals from large, randomly ascertained extended pedigrees who participate in the “Genetics of Brain Structure and Function” study. As affecteds are excluded from analyses, results are not influenced by disease state or medication usage.
Results
Despite having sampled just 6 individuals with schizophrenia, our sample provided 233 individuals at various levels of genetic risk for the disorder. We identified three neurocognitive measures (digit-symbol substitution, facial memory, and emotion recognition) and six medial temporal and prefrontal cortical surfaces associated with liability for schizophrenia.
Conclusions
With our novel analytic approach one can discover and rank endophenotypes for schizophrenia, or any heritable disease, in randomly ascertained pedigrees.
Recommended Citation
Glahn, D. C., Williams, J. T., McKay, D. R., Knowles, E. E., Sprooten, E., Mathias, S. R., Curran, J. E., Kent, J. W., Jr, Carless, M. A., Göring, H. H., Dyer, T. D., Woolsey, M. D., Winkler, A. M., Olvera, R. L., Kochunov, P., Fox, P. T., Duggirala, R., Almasy, L., & Blangero, J. (2015). Discovering schizophrenia endophenotypes in randomly ascertained pedigrees. Biological psychiatry, 77(1), 75–83. https://doi.org/10.1016/j.biopsych.2014.06.027
First Page
75
Last Page
83
Publication Title
Biological psychiatry
DOI
10.1016/j.biopsych.2014.06.027
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
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