Two-dimensional enrichment analysis for mining high-level imaging genetic associations

Xiaohui Yao, Jingwen Yan, Sungeun Kim, Kwangsik Nho, Shannon L. Risacher, Mark Inlow, Jason H. Moore, Andrew J. Saykin, Li Shen, Alzheimer’s Disease Neuroimaging Initiative The Alzheimer’s Disease Neuroimaging Initiative

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Scopus citations

Abstract

Enrichment analysis has been widely applied in the genomewide 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 howgenetic 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 AllenHuman BrainAtlas 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.

Original languageEnglish (US)
Title of host publicationBrain Informatics and Health - 8th International Conference, BIH 2015, Proceedings
EditorsYike Guo Y., Sean Hill S., Karl Friston, Hanchuan Peng, Aldo Faisal A.
PublisherSpringer Verlag
Pages115-124
Number of pages10
ISBN (Print)9783319233437
DOIs
StatePublished - Jan 1 2015
Event8th International Conference on Brain Informatics and Health, BIH 2015 - London, United Kingdom
Duration: Aug 30 2015Sep 2 2015

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume9250
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Other

Other8th International Conference on Brain Informatics and Health, BIH 2015
CountryUnited Kingdom
CityLondon
Period8/30/159/2/15

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Keywords

  • Enrichment analysis
  • Genome wideassociation study
  • Imaging genetics
  • Quantitative trait

ASJC Scopus subject areas

  • Theoretical Computer Science
  • Computer Science(all)

Cite this

Yao, X., Yan, J., Kim, S., Nho, K., Risacher, S. L., Inlow, M., Moore, J. H., Saykin, A. J., Shen, L., & The Alzheimer’s Disease Neuroimaging Initiative, A. D. N. I. (2015). Two-dimensional enrichment analysis for mining high-level imaging genetic associations. In Y. Guo Y., S. Hill S., K. Friston, H. Peng, & A. Faisal A. (Eds.), Brain Informatics and Health - 8th International Conference, BIH 2015, Proceedings (pp. 115-124). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 9250). Springer Verlag. https://doi.org/10.1007/978-3-319-23344-4_12