Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions

Jordan W. Smoller, James S. Acierno, Jerrold F. Rosenbaum, Joseph Biederman, Mark H. Pollack, Susan Meminger, Joel A. Pava, Lisa H. Chadwick, Candace White, Maria Bulzacchelli, Susan A. Slaugenhaupt

Research output: Contribution to journalArticle

Abstract

Family and twin studies have indicated that genes influence susceptibility to panic and phobic anxiety disorders, but the location of the genes involved remains unknown. Animal models can simplify gene-mapping efforts by overcoming problems that complicate human pedigree studies including genetic heterogeneity and high phenocopy rates. Homology between rodent and human genomes can be exploited to map human genes underlying complex traits. We used regions identified by quantitative trait locus (QTL)-mapping of anxiety phenotypes in mice to guide a linkage analysis of a large multiplex pedigree (99 members, 75 genotyped) segregating panic disorder/agoraphobia. Two phenotypes were studied: panic disorder/agoraphobia and a phenotype ("D-type") designed to capture early-onset susceptibility to anxiety disorders. A total of 99 markers across 11 chromosomal regions were typed. Parametric lod score analysis provided suggestive evidence of linkage (lod=2.38) to a locus on chromosome 10q under a dominant model with reduced penetrance for the anxiety-proneness (D-type) phenotype. Nonparametric (NPL) analysis provided evidence of linkage for panic disorder/agoraphobia to a locus on chromosome 12q13 (NPL=4.96, P=0.006). Modest evidence of linkage by NPL analysis was also found for the D-type phenotype to a region of chromosome 1q (peak NPL=2.05, P=0.035). While these linkage results are merely suggestive, this study illustrates the potential advantages of using mouse gene-mapping results and exploring alternative phenotype definitions in linkage studies of anxiety disorder.

Original languageEnglish (US)
Pages (from-to)195-206
Number of pages12
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume105
Issue number2
DOIs
StatePublished - Mar 8 2001

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Keywords

  • Genome scan
  • Linkage analysis
  • Mouse genetics
  • Panic disorder

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Smoller, J. W., Acierno, J. S., Rosenbaum, J. F., Biederman, J., Pollack, M. H., Meminger, S., Pava, J. A., Chadwick, L. H., White, C., Bulzacchelli, M., & Slaugenhaupt, S. A. (2001). Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions. American Journal of Medical Genetics - Neuropsychiatric Genetics, 105(2), 195-206. https://doi.org/10.1002/ajmg.1209