Genome-wide scan for five brain oscillatory phenotypes identifies a new qtl associated with theta eeg band

Brain waves, measured by electroencephalography (EEG), are a powerful tool in the investigation of neurophysiological traits and a noninvasive and cost-effective alternative in the diagnostic of some neurological diseases. In order to identify novel Quantitative Trait Loci (QTLs) for brain wave relative power (RP), we collected resting state EEG data in five frequency bands (d, ¿, a, ß1, and ß2) and genome-wide data in a cohort of 105 patients with late onset Alzheimer’s disease (LOAD), 41 individuals with mild cognitive impairment and 45 controls from Iberia, correcting for disease status. One novel association was found with an interesting candidate for a role in brain wave biology, CLEC16A (C-type lectin domain family 16), with a variant at this locus passing the adjusted genome-wide significance threshold after Bonferroni correction. This finding reinforces the importance of immune regulation in brain function. Additionally, at a significance cutoff value of 5 × 10-6, 18 independent association signals were detected. These signals comprise brain expression Quantitative Loci (eQTLs) in caudate basal ganglia, spinal cord, anterior cingulate cortex and hypothalamus, as well as chromatin interactions in adult and fetal cortex, neural progenitor cells and hippocampus. Moreover, in the set of genes showing signals of association with brain wave RP in our dataset, there is an overrepresentation of loci previously associated with neurological traits and pathologies, evidencing the pleiotropy of the genetic variation modulating brain function.This project is supported by “European Commission” and “European Regional Development Fund” under the project “Análisis y correlación entre el genoma completo y la actividad cerebral para la ayuda en el diagnóstico de la enfermedad de Alzheimer” (Project 1317_AD-EEGWA), (Cooperation Programme INTERREG V-A Spain-Portugal POCTEP 2014–2020) and the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020. Portuguese funds are supporting this work through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). SM, AML, NP and IG are funded by FCT: CEECIND/00684/2017, IF/01262/2014, SFRH/BPD/97414/2013 and CEECIND/02609/2017, respectively. MA is funded by the Grant RYC-2015-18241 from the Spanish Government. Spanish funds are supporting this work through “Ministerio de Ciencia e Innovación–Agencia Estatal de Investigación” and “European Regional Development Fund” under project PGC2018-098214-A-I00 and by “CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)” through “Instituto de Salud Carlos III” co-funded with “European Regional Development Fund” funds