A brain wide association study (BWAS) based on the logistic regression was first developed and applied to a large population of epilepsy patients (168) and healthy controls (136). It was found that the most significant links associated with epilepsy are those bilateral links with regions mainly belonging to the default mode network and subcortex, such as amygdala, fusiform gyrus, inferior temporal gyrus, hippocampus, temporal pole, parahippocampal gyrus, insula, middle occipital gyrus, cuneus. These links were found to have much higher odd ratios than other links, and all of them showed reduced functional couplings in patients compared with controls. Interestingly, with the increasing of the seizure onset frequency or duration of illness, the functional connection between these bilateral regions became further reduced. On the other hand, as a functional compensation and brain plasticity, connections of these bilateral regions to other brain regions were abnormally enhanced and became even much stronger with the increase of the seizure onset frequency. Furthermore, patients had higher network efficiencies than healthy controls, and the seizure onset frequency was found to be positively correlated with the network efficiency. A negative correlation between the bilateral connection and the network efficiency was also observed. To further validate our findings, we then employed our BWAS results in discriminating patients from healthy controls and the leave-one-out accuracy was around 78%. Given the fact that a genome-wide association study with a large cohort has failed to identify any significant association between genes and epilepsy, our study could provide us with a set of endophenotypes for further study.
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