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ILAE Consortium on Complex Epilepsies

The driving principle behind the Consortium is that through collaboration and synergy, we will make more progress towards fully understanding the inherited components of epilepsy than can be achieved by individual groups.

History

The ILAE Consortium on Complex Epilepsies was conceived at the December 2009 meeting of the Genetics Commission of the ILAE. The background at that time was that although epilepsy is a highly heritable group of disorders, there had been modest progress in identifying common variation through association studies. In many ways, epilepsy had lagged behind other common disorders. Through the experience in other diseases, it was clear that the key to successful genome wide association studies (GWAS) was large sample sizes with the merging of independent cohorts for meta-analysis.

There was an open discussion of the proposal at the Rhodes meeting in June 2010 where the committee structure and Charter were developed. By the Rome August 2011 meeting the working committees had been formed and regular teleconferences commenced. A crucial meeting was held at the Royal Society, London, in March 2012, and following that the activities of the Consortium became much more focussed and efficient.

ILAE Consortium on Complex Epilepsies
Consortium meeting, 2012

A formal Charter has been developed and signed by all members. The driving principle behind the Consortium is that through collaboration and synergy, collectively we will make more progress towards fully understanding the inherited components of epilepsy than can be achieved by individual groups. It follows that membership of the Consortium carries advantages for which some sacrifices of autonomy are considered to be a reasonable price – the collective benefits considerably outweigh the individual restrictions. This has indeed turned out to be the case. The first paper of the Consortium was published in Lancet Neurology in September 2014:

Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies
  • Appendix

Membership and Committee Structure

Consortium Charter

The founding contributing groups include: EPICURE, EPIGEN, SANAD/Melbourne collaboration and groups from Philadelphia and Hong Kong. Subsequently the pharmacogenomics cohort from EPICURE has become involved as well as the GenEpa Finnish collaboration.

The current committee structure is as follows:

  • Governance Committee: Sam Berkovic, Dan Lowenstein, Anna-Elina Lehesjoki and Alastair Compston.
  • Strategy Committee: Sam Berkovic (non-voting co-ordinator), Holger Lerche, Bobby Koeleman, Sanjay Sisodiya, Erin Heinzen, Russ Buono, Hakon Hakonarson, Mike Johnson, Terry O’Brien, Patrick Kwan and Larry Baum.
  • Phenotyping Committee: Dan Lowenstein (non-voting co-ordinator) Pasquale Striano, Chantal Depondt, Mike Sperling, Dennis Dlugos, Tony Marson, Patrick Kwan and Wolfram Kunz.
  • Analysis Committee: Gianpiero Cavalleri, Doug Speed, Carolien de Kovel, Zhi Wei, Jonathan Bradfield, Hongsheng Gui, Costin Leu, Stacey Cherny and Christopher Whelan.

A full list of current contributors are listed in the attached Lancet Neurology paper.

Any epilepsy researcher is welcome to join the Consortium. Meetings are held in person once or twice a year, with teleconferences approximately every 2-3 months.

At the present time, analysis has been confined to cohorts that have already undergone SNP genotyping. Funding has been provided by the ILAE to facilitate meetings and a small amount of experimental work. but further major studies will require specific grants.

Future Plans

Future directions and focus will include sub-analyses of the current data set into particular subtypes of epilepsy. Further analyses include collaborating with other large Consortia to look at shared genetic risks for epilepsy and migraine and for epilepsy and neuropsychiatric illnesses, and with the ENIGMA cohort, which looks at the genetic determinants of brain structure. Interrogation of the dataset for variants that may determine anti-epileptic drug side effects such as rash is underway.

Enquiries regarding the Consortium can be directed to or .

 

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