Rights statement: © 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.
Final published version, 2.91 MB, PDF document
Available under license: CC BY: Creative Commons Attribution 4.0 International License
Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Gene prioritization for imaging genetics studies using gene ontology and a stratified false discovery rate approach
AU - Patel, Sejal
AU - Park, Min Tae M.
AU - Chakravarty, M. Mallar
AU - Knight, Jo
AU - Alzheimer's Disease Neuroimaging Initiative
N1 - © 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.
PY - 2016/4/7
Y1 - 2016/4/7
N2 - 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.
AB - 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.
KW - magnetic resonance imaging (MRI)
KW - genome wide association study (GWAS)
KW - gene ontology network
KW - Alzheimer's disease (AD)
KW - stratified false discovery rate (sFDR)
KW - imaging genetics
U2 - 10.3389/fninf.2016.00014
DO - 10.3389/fninf.2016.00014
M3 - Journal article
C2 - 27092072
VL - 10
JO - Frontiers in Neuroinformatics
JF - Frontiers in Neuroinformatics
SN - 1662-5196
M1 - 14
ER -