About the Initiative
The field of epilepsy genetics is rapidly changing, as new genes associated with epilepsy are regularly identified. People with epilepsy who have had their whole exomes sequenced in a diagnostic lab but did not receive a genetic diagnosis have their information submitted to EGI by their physician. Over a five-year period, 2015 – 2020, information including clinical and genetic data from people with epilepsy, and in many cases, their families, was submitted by physicians at EGI enrollment sites across the globe.
During the active phase of EGI, the data were analyzed every six months to determine if a previously unknown mutation (genetic variant) may be the cause of a person’s epilepsy, and any evidence of a genetic cause of a participant’s epilepsy was reported back to the person’s physician. The anonymized whole exome data will continue to be analyzed by EGI investigators at Columbia University, some enrollment sites, and for cutting-edge research projects worldwide.
Initiative Outcomes
Nearly 50% of people with epilepsy don’t know the cause of their epilepsy, but genetic research is changing that. What makes the EGI database unique and valuable is that it includes de-identified clinical data of a person with epilepsy along with their genetic data. It also includes a large amount of trio data, in other words, genetic information from a child with epilepsy along with that of the child’s parents.
By making this database available to epilepsy researchers around the world, EGI will continue to make a difference for people and families impacted by epilepsy well into the future.
Since 2015, EGI has produced the following results:
In total, 364 patients that did not have a clear genetic diagnosis through clinical whole exome sequencing were enrolled into EGI. EGI has provided new or modified genetic diagnoses for a total of 34 patients. In 16 of the 34 cases, EGI identified a mutation in a gene that was not initially found by the initial whole exome sequencing done at a genetic testing laboratory. The genes identified are as follows:
In the remaining 18 cases, a genetic mutation was identified on the initial testing report but it was not conclusively considered disease causing at that time. Reanalysis of the whole exome sequence data through EGI combined with the additional knowledge uncovered in the field of epilepsy genetics at the time of reanalysis, clarified the pathogenicity of these gene mutations. The EGI team was able to report findings on the following genes back to the patient’s original physician:
Reanalysis due to EGI improved the diagnostic yield of the original whole exome sequencing by 9.3%. This illustrates the importance of reanalysis of genetic data over time to discover new diagnoses for individuals with epilepsy but also, to aid in identifying new evidence that some genetic mutations do not contribute to an individuals epilepsy, which may save patients from unnecessary interventions.
Epilepsy Genetics Initiative (EGI) Database
The EGI database includes raw exome sequence data files (BAM/FASTQ) and the accompanying de-identified clinical information:
- Demographics (date of birth, age, gender, race and ethnicity)
- Family history of epilepsy and other relevant medical conditions
- Birth and neonatal history
- Epilepsy history (risk factors, age of first seizure, seizure type(s), EEG results and neuroimaging results)
- Development and cognitive function information (development delays, IQ)
- Other medical conditions that are present in the patient
- Abnormal genetic or metabolic testing
- Epilepsy classification, syndrome, etiology, response to treatments and outcome
- Participation in any other genetics databases or studies (e.g. Epi4K, EPGP, PERC, REN, SeizureTracker, etc.)
Data in EGI, including exome sequence data and clinical information, does not contain any identifying information. Patient data are assigned a study number and only the treating physician and EGI genetic counseling team know which number is assigned to each patient.
Whats next for EGI?
EGI is designed to be a community resource, and the whole exome data within the database is available to the entire research community through two different portals:
- The EGI Data Browser, developed by Columbia University (New York City, New York USA), is a catalogue of genetic variants identified from patients sequenced for their diagnosis of epilepsy. The database includes single nucleotide substitution variants (SNVs) and insertion and deletion (indels) variants.
- The Database of Genotypes and Phenotypes (dbGaP) is a National Institutes of Health (NIH) sponsored repository charged to archive, curate and distribute information produced by studies focused on genetics. De-identified genetic information from EGI is available to researchers who request access to the data.
Researchers will only receive de-identified data with no information that can be linked back to patients or family members.
The EGI initiative has reinforced CURE Epilepsy’s leadership in epilepsy genetics research through:
- Facilitating the collection of whole exome data to advance research, both US-based and abroad and making it available for research.
- Identifying new genes associated with epilepsy as a result of reanalysis of exome data.
- Identifying treatments to try, treatments to avoid, and risk for SUDEP for certain genetic cases of epilepsy.
- Elevating awareness and funding for genetic research into the causes of epilepsy.
- Helping doctors diagnose patients who have epilepsy.
- Advancing precision medicine in epilepsy.
Related Research
Our Research Initiatives
Since its inception, CURE Epilepsy has been at the forefront of epilepsy research, raising over $99 million to fund research and other programs that will lead the way to a cure for epilepsy.
See our other Research Initiatives