Discovery and replication of gene influences on brain structure using LASSO regression

Kohannim, Omid, Hibar, Derrek P., Stein, Jason L., Jahanshad, Neda, Hua, Xue, Rajagopalan, Priya, Toga, Arthur W., Jack Jr., Clifford R., Weiner, Michael W., de Zubicaray, Greig I., McMahon, Katie L., Hansell, Narelle K., Martin, Nicholas G., Margaret J. Wright, Thompson, Paul M. and The Alzheimer’s Disease Neuroimaging Initiative (2012) Discovery and replication of gene influences on brain structure using LASSO regression. Frontiers in Neuroscience, 6 AUG: 115.1-115.13. doi:10.3389/fnins.2012.00115

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Author Kohannim, Omid
Hibar, Derrek P.
Stein, Jason L.
Jahanshad, Neda
Hua, Xue
Rajagopalan, Priya
Toga, Arthur W.
Jack Jr., Clifford R.
Weiner, Michael W.
de Zubicaray, Greig I.
McMahon, Katie L.
Hansell, Narelle K.
Martin, Nicholas G.
Margaret J. Wright
Thompson, Paul M.
The Alzheimer’s Disease Neuroimaging Initiative
Title Discovery and replication of gene influences on brain structure using LASSO regression
Journal name Frontiers in Neuroscience   Check publisher's open access policy
ISSN 1662-4548
1662-453X
Publication date 2012-08
Sub-type Article (original research)
DOI 10.3389/fnins.2012.00115
Open Access Status DOI
Volume 6
Issue AUG
Start page 115.1
End page 115.13
Total pages 13
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2013
Language eng
Formatted abstract
We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8 ± 2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.
Keyword Neuroimaging
MRI
Imaging genetics
GWAS
LASSO
MACROD2
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Fri, 14 Sep 2012, 15:38:43 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging