Predicting white matter integrity from multiple common genetic variants

Kohannim, O., Jahanshad, N., Braskie, M. N., Stein, J. L., Chiang, M. C., Reese, A. H., Hibar, D. P., Toga, A. W., McMahon, K. L., de Zubicaray, G. I., Medland, S. E., Montgomery, G. W., Martin, N. G., Wright, M. J., & Thompson, P. M. (2012) Predicting white matter integrity from multiple common genetic variants. Neuropsychopharmacology, 37(9), pp. 2012-2019.

View at publisher


Several common genetic variants have recently been discovered that appear to influence white matter microstructure, as measured by diffusion tensor imaging (DTI). Each genetic variant explains only a small proportion of the variance in brain microstructure, so we set out to explore their combined effect on the white matter integrity of the corpus callosum. We measured six common candidate single-nucleotide polymorphisms (SNPs) in the COMT, NTRK1, BDNF, ErbB4, CLU, and HFE genes, and investigated their individual and aggregate effects on white matter structure in 395 healthy adult twins and siblings (age: 20-30 years). All subjects were scanned with 4-tesla 94-direction high angular resolution diffusion imaging. When combined using mixed-effects linear regression, a joint model based on five of the candidate SNPs (COMT, NTRK1, ErbB4, CLU, and HFE) explained ∼ 6% of the variance in the average fractional anisotropy (FA) of the corpus callosum. This predictive model had detectable effects on FA at 82% of the corpus callosum voxels, including the genu, body, and splenium. Predicting the brain's fiber microstructure from genotypes may ultimately help in early risk assessment, and eventually, in personalized treatment for neuropsychiatric disorders in which brain integrity and connectivity are affected.

Impact and interest:

29 citations in Scopus
Search Google Scholar™
27 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 85800
Item Type: Journal Article
Refereed: No
Keywords: brain structure, DTI, genetic profiles, genetics, neuroimaging, prediction
DOI: 10.1038/npp.2012.49
ISSN: 1740-634X
Divisions: Current > QUT Faculties and Divisions > Faculty of Law
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 American College of Neuropsychopharmacology
Deposited On: 28 Sep 2015 06:52
Last Modified: 30 Sep 2015 01:04

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page