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

Jahanshad, N., Hibar, D. P., Ryles, A., Toga, A. W., McMahon, K. L., de Zubicaray, G. I., Hansell, N. K., Montgomery, G. W., Martin, N. G., Wright, M. J., & Thompson, P. 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: May 2-5, 2012, Barcelona, Spain, IEEE, Barcelona, Spain, pp. 542-545.

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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 70×70 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. © 2012 IEEE.

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ID Code: 85777
Item Type: Conference Paper
Refereed: Yes
Keywords: cortical surfaces, genetics, high angular resolution diffusion imaging (HARDI), human connectome, twin modeling
DOI: 10.1109/ISBI.2012.6235605
ISBN: 9781457718571
ISSN: 1945-7928
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copright 2012 IEEE
Deposited On: 04 Sep 2015 01:29
Last Modified: 06 Sep 2015 23:25

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