**2005 Report submitted by Benchmark Steward(s):**

Ruth Ottman, Ph.D. (Columbia University)

**Background of the benchmark goal:**

Most epilepsy is not consistent with Mendelian modes of inheritance. The
genes that influence risk in the majority of patients are likely to have
small effects, interacting with the effects of environmental factors.
Identification of such genes requires very large numbers of patients.
Thus a collaborative study, with the highest quality of methods for
phenotype and genotype analysis, is essential to move the field forward.

**Current status of field:**

Allelic association studies are being performed by many separate groups,
and published at a rapidly increasing rate. Most of these studies are
underpowered. Consequently, about half of the reported findings are
positive, and half negative, and no association has been consistently
confirmed.

**Activities update:**

Dan Lowenstein spearheaded a multi-institutional effort to conduct a
state-of-the-art study of genes in genetically complex epilepsies. The
result was a collaboration of 14 institutions throughout the U.S., and a
well-designed, adequately powered study to address the most pressing
issues in epilepsy genetics (e.g., gene discovery in genetically complex
epilepsies, genes influencing treatment response, and the role of
somatic mutations). The proposal for this project, which will include
5,000 superbly well-characterized patients and 15,000 controls, was
submitted to NIH for review.

**Top priorities for next 5-10 years:**

-   Identification of genetic polymorphisms that influence risk for
    genetically complex epilepsies and for response to treatments.

-   Development and evaluation of methods to use genetic information to
    develop new treatments and tailor them to specific patients.

-   Development of new paradigms for epilepsy classification that
    reflect shared and distinct genetic mechanisms.

**Roadblocks to progress:**

Study designs involving large numbers of patients, with state-of-the-art
genomic analysis and clinical characterization, are extremely expensive.

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