Genome-Wide Linkage Analysis of Human Auditory Cortical Activation Suggests Distinct Loci on Chromosomes 2, 3, and 8

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Volume Title
School of Science | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Date
2012
Major/Subject
Mcode
Degree programme
Language
en
Pages
14511-14518
Series
Journal of Neuroscience, Volume 32, Issue 42
Abstract
Neural processes are explored through macroscopic neuroimaging and microscopic molecular measures, but the two levels remain primarily detached. The identification of direct links between the levels would facilitate use of imaging signals as probes of genetic function and, vice versa, access to molecular correlates of imaging measures. Neuroimaging patterns have been mapped for a few isolated genes, chosen based on their connection with a clinical disorder. Here we propose an approach that allows an unrestricted discovery of the genetic basis of a neuroimaging phenotype in the normal human brain. The essential components are a subject population that is composed of relatives and selection of a neuroimaging phenotype that is reproducible within an individual and similar between relatives but markedly variable across a population. Our present combined magnetoencephalography and genome-wide linkage study in 212 healthy siblings demonstrates that auditory cortical activation strength is highly heritable and, specifically in the right hemisphere, regulated oligogenically with linkages to chromosomes 2q37, 3p12, and 8q24. The identified regions delimit as candidate genes TRAPPC9, operating in neuronal differentiation, and ROBO1, regulating projections of thalamocortical axons. Identification of normal genetic variation underlying neurophysiological phenotypes offers a non-invasive platform for an in-depth, concerted capitalization of molecular and neuroimaging levels in exploring neural function.
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Keywords
neural processes, macroscopic neuroimaging, microscopic molecular measures
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Citation
Renvall, H. & Salmela, E. & Vihla, M. & Illman, M. & Leinonen, E. & Kere, J. & Salmelin, Riitta. 2012. Genome-Wide Linkage Analysis of Human Auditory Cortical Activation Suggests Distinct Loci on Chromosomes 2, 3, and 8. Journal of Neuroscience. Volume 32, Issue 42. P. 14511-14518. ISSN 0270-6474 (printed). DOI: 10.1523/jneurosci.1483-12.2012.