The genetics of commonly used EEG parameters: Results from the ENIGMA-EEG working group

ENIGMA-EEG was created in order to combine forces to find the genetic variants that cause this genetic variation. Our goal is to understand how genetic liability affects the brain and results in psychiatric disorders like OCD, ADHD and autism and other disorders of the brain like epilepsy. It may hardly come as a surprise that the GWAS for these brain disorders mostly point to genes expressed in excitatory and inhibitory neurons. In our view, this is where EEG steps in: to explain how these liability genes affect brain function. For this, we perform GWAS of EEG parameters using the meta-analytic approach, where each participating cohort performs their analyses on-site using our standardized cleaning and analysis protocols, which are then meta-analyzed by the lead analyst group.

ENIGMA-EEG largely focuses on oscillatory activity, as these oscillations depend on excitatory and inhibitory feedback mechanisms in the brain that are affected by the genetic variants. Twin studies have found that individual variation of these EEG parameters is often highly heritable. For example, the power of alpha (10 Hz) oscillations over frontal brain areas is more heritable than standing height. Connectivity measures and autocorrelational patterns and microstates also show substantial genetic contributions. In addition, our understanding of how oscillatory activity shapes our mental world (functional as well as dysfunctional) is vastly increasing. Deep brain recording studies confirm that oscillatory activity is crucial for communication in the brain and correlate with symptoms, aberrant cognition, and disorder-like states. In rodent models, actively inducing oscillatory activity using optogenetics proves that oscillations are indeed causal to behavior.

I will show the results from ENIGMA-EEG and how these results can be used to inform the large-scale GWAS. I will show how chromosomal region 3p21.1--linked to bipolar disorder and depression--is linked to alpha oscillations; how hippocampal GABRA2 expression is linked to beta oscillations, both independently linked to alcohol use disorders. Beta oscillations are (genetically) linked to epilepsy, a surprisingly novel finding. In addition, I will present our new protocols and preliminary results from GWAS of brain connectivity, oscillatory dynamic activity, and theta-beta ratio (often linked to ADHD).

Dirk J.A. Smit

My research takes place on the edge between genetics and the brain. I lead several genetic consortia, including the OC symptom group of the Psychiatric Genomics Consortium, the Hoarding Symptom GWAS, and of course ENIGMA-EEG, tying all these to brain expression using TWAS, E-MAGMA and related techniques. We develop genetic factor models to explain liability substance of disorders, and how these are confounded with socioeconomic status. In addition, I am involved in research of brain function in OCD with deep brain recordings, where we use machine learning to predict symptomatic states of the patients.