Abstract
Enrichment analysis has been widely applied in the genome-wide association studies (GWAS), where gene sets corresponding to biological pathways are examined for significant associations with a phenotype to help increase statistical power and improve biological interpretation. In this work, we expand the scope of enrichment analysis into brain imaging genetics, an emerging field that studies how genetic variation influences brain structure and function measured by neuroimaging quantitative traits (QT). Given the high dimensionality of both imaging and genetic data, we propose to study Imaging Genetic Enrichment Analysis (IGEA), a new enrichment analysis paradigm that jointly considers meaningful gene sets (GS) and brain circuits (BC) and examines whether any given GS-BC pair is enriched in a list of gene-QT findings. Using gene expression data from Allen Human Brain Atlas and imaging genetics data from Alzheimer’s Disease Neuroimaging Initiative as test beds, we present an IGEA framework and conduct a proof-of-concept study. This empirical study identifies 12 significant high level two dimensional imaging genetics modules. Many of these modules are relevant to a variety of neurobiological pathways or neurodegenerative diseases, showing the promise of the proposal framework for providing insight into the mechanism of complex diseases.
L. Shen—This work was supported by NIH R01 LM011360, U01 AG024904 (details available at http://adni.loni.usc.edu), RC2 AG036535, R01 AG19771, P30 AG10133, and NSF IIS-1117335 at IU, and by NIH R01 LM011360, R01 LM009012, and R01 LM010098 at UPenn.
Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
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Yao, X. et al. (2015). Two-Dimensional Enrichment Analysis for Mining High-Level Imaging Genetic Associations. In: Guo, Y., Friston, K., Aldo, F., Hill, S., Peng, H. (eds) Brain Informatics and Health. BIH 2015. Lecture Notes in Computer Science(), vol 9250. Springer, Cham. https://doi.org/10.1007/978-3-319-23344-4_12
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