Genetic research on human epilepsy is advancing rapidly, with more than 20 genes already identified in rare Mendelian epilepsy syndromes, and major efforts underway to identify genes in the more common """"""""genetically complex"""""""" epilepsies. Clinical genetic testing is available for several epilepsy syndromes in which genes have been identified, and clinicians who treat patients with epilepsy widely believe that genetic testing wil be helpful for their patients. However, almost no empirical data are available on the psychosocial impact of genetic information on people with epilepsy and their family members. Research in this area is urgently needed because of the significant psychosocial dimensions of living with epilepsy, which include stigma, discrimination, reduced rates of marriage and reproduction, and reduced health-related quality of life. This study will address this gap by researching psychosocial outcomes and their relations with genetic attributions and actual genetic test results in families containing multiple individuals with epilepsy. The study involves two parts. First, we will carry out a survey of 1053 individuals from 115 families, to evaluate stated preferences and anticipated benefits and harms of genetic testing, and measures of quality of life, epilepsy-related stigma, and their predictors. Second, we will offer clinical geneic testing to individuals in a subset of families (21 families, containing 195 individuals) with a for of temporal lobe epilepsy initially described by our group, """"""""autosomal dominant partial epilepsy with auditory features"""""""" (ADPEAF). Half of these families were previously found to have mutations in the LGI1 gene on chromosome 10. Although study participants have been informed about this gene discovery in aggregate (through a newsletter), they have never been offered individual results. We recently established a clinical genetic test for LGI1 in our institution's Clinical Laboratory Improvement Act (CLIA)-certified laboratory, and we will we will offer clinical genetic testing to individuals in families with ADPEAF, evaluate actual uptake and its predictors, and follow prospectively the impact of genetic information on individuals who choose to be tested. We will also carry out qualitative interviews on a subset of individuals offered testing, t explore in greater depth the range of issues related to receiving genetic information in epilepsy. No previous quantitative study has investigated the psychosocial impact of genetic information on individuals with epilepsy and their family members;hence the results should be extremely valuable for planning of genetic services that maximize benefit and minimize harm in this disorder.

Public Health Relevance

This investigation focuses on the psychosocial impact of genetic information on individuals with epilepsy and their family members. Research in this area is urgently needed because of the significant psychosocial dimensions of living with epilepsy, which include stigma, discrimination, reduced rates of marriage and reproduction, and reduced health-related quality of life. The ways in which genetic information might alter the experience of living with epilepsy are unclear.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS078419-01
Application #
8276345
Study Section
Special Emphasis Panel (SEIR)
Program Officer
Whittemore, Vicky R
Project Start
2012-04-01
Project End
2016-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$618,835
Indirect Cost
$231,062
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Ottman, Ruth; Freyer, Catharine; Mefford, Heather C et al. (2018) Return of individual results in epilepsy genomic research: A view from the field. Epilepsia 59:1635-1642
Epi4K Consortium (2017) Phenotypic analysis of 303 multiplex families with common epilepsies. Brain 140:2144-2156
Sorge, Shawn T; Hesdorffer, Dale C; Phelan, Jo C et al. (2016) Depression and genetic causal attribution of epilepsy in multiplex epilepsy families. Epilepsia 57:1643-1650
Caminiti, Courtney B; Hesdorffer, Dale C; Shostak, Sara et al. (2016) Parents' interest in genetic testing of their offspring in multiplex epilepsy families. Epilepsia 57:279-87
Louis, Elan D; Clark, Lorraine; Ottman, Ruth (2016) Familial Aggregation and Co-Aggregation of Essential Tremor and Parkinson's Disease. Neuroepidemiology 46:31-6
Liu, Xinmin; Hernandez, Nora; Kisselev, Sergey et al. (2016) Identification of candidate genes for familial early-onset essential tremor. Eur J Hum Genet 24:1009-15
Sabatello, Maya; Phelan, Jo C; Hesdorffer, Dale C et al. (2015) Genetic causal attribution of epilepsy and its implications for felt stigma. Epilepsia 56:1542-50
Dazzo, Emanuela; Fanciulli, Manuela; Serioli, Elena et al. (2015) Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy. Am J Hum Genet 96:992-1000
Callaghan, Brian; Choi, Hyunmi; Schlesinger, Malka et al. (2014) Increased mortality persists in an adult drug-resistant epilepsy prevalence cohort. J Neurol Neurosurg Psychiatry 85:1084-90

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