Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {Leu, C and Stevelink, R and Smith, AW and Goleva, SB and Kanai, M and Ferguson, L and Campbell, C and Kamatani, Y and Okada, Y and Sisodiya, SM and Cavalleri, GL and Koeleman, BPC and Lerche, H and Jehi, L and Davis, LK and Najm, IM and Palotie, A and Daly, MJ and Busch, RM and Epi25, Consortium and Lal, D},
doi = {brain/awz292},
journal = {Brain},
pages = {3473--3481},
title = {Polygenic burden in focal and generalized epilepsies.},
url = {},
volume = {142},
year = {2019}

RIS format (EndNote, RefMan)

AB - Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10-15; Cleveland: P = 2.85×10-4; Finnish-ancestry Epi25: P = 1.80×10-4) or population controls (Epi25: P = 2.35×10-70; Cleveland: P = 1.43×10-7; Finnish-ancestry Epi25: P = 3.11×10-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10-19; Cleveland: P = 1.69×10-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish Europ
AU - Leu,C
AU - Stevelink,R
AU - Smith,AW
AU - Goleva,SB
AU - Kanai,M
AU - Ferguson,L
AU - Campbell,C
AU - Kamatani,Y
AU - Okada,Y
AU - Sisodiya,SM
AU - Cavalleri,GL
AU - Koeleman,BPC
AU - Lerche,H
AU - Jehi,L
AU - Davis,LK
AU - Najm,IM
AU - Palotie,A
AU - Daly,MJ
AU - Busch,RM
AU - Epi25,Consortium
AU - Lal,D
DO - brain/awz292
EP - 3481
PY - 2019///
SP - 3473
TI - Polygenic burden in focal and generalized epilepsies.
T2 - Brain
UR -
UR -
UR -
VL - 142
ER -