Gene prioritization for imaging genetics studies using gene ontology and a stratified false discovery rate approach

Patel, Sejal and Park, Min Tae M. and Chakravarty, M. Mallar and Knight, Jo (2016) Gene prioritization for imaging genetics studies using gene ontology and a stratified false discovery rate approach. Frontiers in Neuroinformatics, 10: 14. ISSN 1662-5196

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Imaging genetics is an emerging field in which the association between genes and neuroimaging-based quantitative phenotypes are used to explore the functional role of genes in neuroanatomy and neurophysiology in the context of healthy function and neuropsychiatric disorders. The main obstacle for researchers in the field is the high dimensionality of the data in both the imaging phenotypes and the genetic variants commonly typed. In this article, we develop a novel method that utilizes Gene Ontology, an online database, to select and prioritize certain genes, employing a stratified false discovery rate (sFDR) approach to investigate their associations with imaging phenotypes. sFDR has the potential to increase power in genome wide association studies (GWAS), and is quickly gaining traction as a method for multiple testing correction. Our novel approach addresses both the pressing need in genetic research to move beyond candidate gene studies, while not being overburdened with a loss of power due to multiple testing. As an example of our methodology, we perform a GWAS of hippocampal volume using both the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA2) and the Alzheimer's Disease Neuroimaging Initiative datasets. The analysis of ENIGMA2 data yielded a set of SNPs with sFDR values between 10 and 20%. Our approach demonstrates a potential method to prioritize genes based on biological systems impaired in a disease.

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Journal Article
Journal or Publication Title:
Frontiers in Neuroinformatics
Additional Information:
© 2016 Patel, Park, The Alzheimer's Disease Neuroimaging Initiative, Chakravarty and Knight. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords:
?? magnetic resonance imaging (mri)genome wide association study (gwas)gene ontology networkalzheimer's disease (ad)stratified false discovery rate (sfdr)imaging geneticsbiomedical engineeringcomputer science applicationsneuroscience (miscellaneous) ??
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Deposited On:
08 Jun 2016 09:16
Last Modified:
18 Dec 2023 01:38