1995 OCF Grant

A molecular genetic analysis of early-onset obsessive compulsive disorder

Gregory L. Hanna, MD

University of Michigan (Ann Arbor, MI)

At the time of this grant, interest in research on the genetic basis of OCD was growing. With greater understanding of the roles that specific genetic variants play in the development of OCD, early detection and treatment could be advanced. Studies of families with several affected relatives became especially useful in understanding genetic factors in OCD.

Dr. Hanna and his team aimed to identify chromosomal regions likely to contain risk alleles (gene variations) that are linked with early-onset OCD. They conducted a series of tests (genome scans, detailed mapping of certain chromosomes, and interviews) with a total of 66 participants coming from seven families each having several members with pediatric OCD. Of these participants, 32 had a lifetime diagnosis of OCD, and three of the seven families had a history of Tourette syndrome, a related condition characterized by motor and vocal tics. Dense mapping of chromosomes 2, 9, and 16 suggested the potential role of a number of genetic markers, including a deletion of part of chromosome 9. The results of this project demonstrated the need for further genetic studies that included much larger samples, to continue exploring how genes affect the development of OCD with more accuracy. This grant-funded project eventually helped launch the first genome-wide linkage study of OCD and inspired other genetic research, including the first studies of how the glutamate transporter gene (SLC1A1) may be involved in OCD.

 

Related Publications:

Dickel, D. E., Veenstra-VanderWeele, J., Cox, N. J., Wu, X., Fischer, D. J., Van Etten-Lee, M., Himle, J. A., Leventhal, B. L., Cook, E. H., Jr, & Hanna, G. L. (2006). Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Archives of General Psychiatry63(7), 778–785. doi:10.1001/archpsyc.63.7.778

Hanna, G. L., Veenstra-VanderWeele, J., Cox, N. J., Boehnke, M., Himle, J. A., Curtis, G. C., Leventhal, B. L., & Cook, E. H., Jr (2002). Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. American Journal of Medical Genetics114(5), 541–552. doi:10.1002/ajmg.10519

Hanna, G. L., Veenstra-Vanderweele, J., Cox, N. J., Van Etten, M., Fischer, D. J., Himle, J. A., Bivens, N. C., Wu, X., Roe, C. A., Hennessy, K. A., Dickel, D. E., Leventhal, B. L., & Cook, E. H., Jr (2007). Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder. Biological Psychiatry62(8), 856–862. doi:10.1016/j.biopsych.2007.01.008

Mathews, C. A., Badner, J. A., Andresen, J. M., Sheppard, B., Himle, J. A., Grant, J. E., Williams, K. A., Chavira, D. A., Azzam, A., Schwartz, M., Reus, V. I., Kim, S. W., Cook, E. H., & Hanna, G. L. (2012). Genome-wide linkage analysis of obsessive-compulsive disorder implicates chromosome 1p36. Biological Psychiatry72(8), 629–636. doi:10.1016/j.biopsych.2012.03.037