Alcohol Reverses the Effects of KCNJ6 (GIRK2) Noncoding Variants on Excitability of Human Glutamatergic Neurons

People diagnosed with alcohol use disorder have been studied to identify genes linked with their diagnosis as well as other measurements such as EEG/behavioral tests.  Previous work has linked these EEG measurements with variations in and near KCNJ6, a gene encoding a potassium channel protein.  To study this, we prepared induced pluripotent stem cells using blood cells from people with and without the gene variants and then prepared human neurons.  Gene variations do not change the potassium channel protein, but here we show that they affect functional levels of the potassium channel, in turn changing neuron excitability.  Unexpectedly, alcohol exposure reverses the effect, predicting that people with this genetic variation may experience a unique response to drinking. 

Popova, D., Gameiro-Ros, I., Youssef, M.M. et al. Alcohol reverses the effects of KCNJ6(GIRK2) noncoding variants on excitability of human glutamatergic neurons. Mol Psychiatry (2022).