Discovery of genes that affect human brain connectivity: a genome-wide analysis of the connectome

Jahanshad, Neda, Hibar, Derrek, Ryles, April, Toga, Arthur W., McMahon, Katie L., de Zubicaray, Greig I., Hansel, Narelle K., Montgomery, Grant W., Martin, Nicholas G., Wright, Margaret J. and Thompson, Paul M. (2012). Discovery of genes that affect human brain connectivity: a genome-wide analysis of the connectome. In: 2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro: Proceedings. 9th International Symposium on Biomedical Imaging, Barcelona, Spain, (542-545). 2-5 May 2012. doi:10.1109/ISBI.2012.6235605

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Author Jahanshad, Neda
Hibar, Derrek
Ryles, April
Toga, Arthur W.
McMahon, Katie L.
de Zubicaray, Greig I.
Hansel, Narelle K.
Montgomery, Grant W.
Martin, Nicholas G.
Wright, Margaret J.
Thompson, Paul M.
Title of paper Discovery of genes that affect human brain connectivity: a genome-wide analysis of the connectome
Conference name 9th International Symposium on Biomedical Imaging
Conference location Barcelona, Spain
Conference dates 2-5 May 2012
Proceedings title 2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro: Proceedings   Check publisher's open access policy
Journal name Proceedings - International Symposium on Biomedical Imaging   Check publisher's open access policy
Place of Publication Piscataway, NJ, United States
Publisher IEEE (Institute for Electrical and Electronic Engineers)
Publication Year 2012
Sub-type Fully published paper
DOI 10.1109/ISBI.2012.6235605
ISBN 9781457718571
ISSN 1945-7928
Start page 542
End page 545
Total pages 4
Collection year 2013
Language eng
Abstract/Summary Human brain connectivity is disrupted in a wide range of disorders – from Alzheimer’s disease to autism – but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70x70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration.
Keyword Genetics
High angular resolution diffusion imaging (HARDI)
Cortical surfaces
Twin modeling
Human connectome
Q-Index Code E1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Thu, 16 Feb 2012, 10:37:10 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging