Stevelink, Remi; Koeleman, Bobby PC; Sisodiya, Sanjay M; International League Against Epilepsy Consortium on Complex epil, .; (2023) Distinct genetic basis of common epilepsies and structural magnetic resonance imaging measures. Epilepsia , 64 (5) e82-e86. 10.1111/epi.17529.

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Abstract

Focal and generalized epilepsies are associated with robust differences in MRI measures of subcortical structures, grey matter and white matter. However, it is unknown whether such structural brain differences reflect the cause or consequence of epilepsy or its treatment. Analyses of common genetic variants underlying both common epilepsy and variability in structural brain measures can give further insights, since such inherited variants are not influenced by disease or treatment. Here, we performed genetic correlation analyses using data from the largest genome-wide association study (GWAS) on common epilepsy (n=27,559 cases and 42,436 controls) and GWAS on MRI measures of white (n=33,292) or grey matter (n=51,665). We did not detect any significant genetic correlation between any type of common epilepsy and any of 280 measures of grey matter, white matter or subcortical structures. These results suggest that there are distinct genetic bases underlying risk of common epilepsy and for structural brain measures. This would imply that the genetic basis of normal structural brain variation is unrelated to that of common epilepsy. Structural changes in epilepsy could rather be the consequence of epilepsy, its comorbidities or its treatment, offering a cumulative record of disease.

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