Evidence for genetic regulation of the human parieto-occipital 10-Hz rhythmic activity.
Several functional and morphological brain measures are partly under genetic control. The identification of direct links between neuroimaging signals and corresponding genetic factors can reveal cellular-level mechanisms behind the measured macroscopic signals and contribute to the use of imaging signals as probes of genetic function. To uncover possible genetic determinants of the most prominent brain signal oscillation, the parieto-occipital 10-Hz alpha rhythm, we measured spontaneous brain activity with magnetoencephalography in 210 healthy siblings while the subjects were resting, with eyes closed and open. The reactivity of the alpha rhythm was quantified from the difference spectra between the two conditions. We focused on three measures: peak frequency, peak amplitude and the width of the main spectral peak. In accordance with earlier electroencephalography studies, spectral peak amplitude was highly heritable (h(2)  > 0.75). Variance component-based analysis of 28 000 single-nucleotide polymorphism markers revealed linkage for both the width and the amplitude of the spectral peak. The strongest linkage was detected for the width of the spectral peak over the left parieto-occipital cortex on chromosome 10 (LOD = 2.814, nominal P < 0.03). This genomic region contains several functionally plausible genes, including GRID1 and ATAD1 that regulate glutamate receptor channels mediating synaptic transmission, NRG3 with functions in brain development and HRT7 involved in the serotonergic system and circadian rhythm. Our data suggest that the alpha oscillation is in part genetically regulated, and that it may be possible to identify its regulators by genetic analyses on a realistically modest number of samples.
Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, PO Box 63, FI-00014, Helsinki, Finland.|Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland.
Elina
E
Salmela
Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.|Aalto Neuroimaging, MEG Core, Aalto University, Espoo, Finland.|Clinical Neurosciences, Neurology, University of Helsinki and Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
Hanna
H
Renvall
Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.|Aalto Neuroimaging, MEG Core, Aalto University, Espoo, Finland.
Jan
J
Kujala
Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, PO Box 63, FI-00014, Helsinki, Finland.
Osmo
O
Hakosalo
Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.|Aalto Neuroimaging, MEG Core, Aalto University, Espoo, Finland.
Mia
M
Illman
Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.|Aalto Neuroimaging, MEG Core, Aalto University, Espoo, Finland.|City of Helsinki Health Centre, Helsinki, Finland.
Minna
M
Vihla
Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, PO Box 63, FI-00014, Helsinki, Finland.|Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland.
Eira
E
Leinonen
Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.|Aalto Neuroimaging, MEG Core, Aalto University, Espoo, Finland.
Riitta
R
Salmelin
Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, PO Box 63, FI-00014, Helsinki, Finland.|Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland.|Science for Life Laboratory, Karolinska Institutet, Solna, Sweden.
Juha
J
Kere
D000074183:ATPases Associated with Diverse Cellular Activities / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000513:Alpha Rhythm / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D005260:Female; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D020880:Neuregulins / Q000235:genetics; D009778:Occipital Lobe / Q000502:physiology*; D010296:Parietal Lobe / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide
D048868:Adaptor Proteins, Signal Transducing; C409587:GRAP2 protein, human; C486357:NRG3 protein, human; D020880:Neuregulins; C000613643:ATAD1 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
alpha rhythm; heritability; linkage study; magnetoencephalography