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Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder

Authors

  • Laura M. Hodges,

    1. Department of Psychiatry, Institute for Human Genetics, University of California, San Francisco, California
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  • Myrna M. Weissman,

    1. Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, Columbia, New York
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  • Fatemeh Haghighi,

    1. Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, Columbia, New York
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  • Ramiro Costa,

    1. Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, Columbia, New York
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  • Oscar Bravo,

    1. Department of Psychiatry, Institute for Human Genetics, University of California, San Francisco, California
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  • Oleg Evgrafov,

    1. Department of Psychiatry and Behavioral Sciences, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • James A. Knowles,

    1. Department of Psychiatry and Behavioral Sciences, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California
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  • Abby J. Fyer,

    1. Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, Columbia, New York
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  • Steven P. Hamilton

    Corresponding author
    1. Department of Psychiatry, Institute for Human Genetics, University of California, San Francisco, California
    • University of California, San Francisco, 401 Parnassus Avenue, Box NGL, San Francisco, CA 94143-0984.
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  • Please cite this article as follows: Hodges LM, Weissman MM, Haghighi F, Costa R, Bravo O, Evgrafov O, Knowles JA, Fyer AJ, Hamilton SP. 2008. Association and Linkage Analysis of Candidate Genes GRP, GRPR, CRHR1, and TACR1 in Panic Disorder. Am J Med Genet Part B 150B:65–73.

Abstract

Panic disorder (PD) is a debilitating anxiety disorder, characterized by recurrent episodes of intense fear that are accompanied by autonomic and psychological symptoms leading to behavioral impairment. Basic research implicates neuropeptide-signaling genes in the modulation of anxiety and stress. The genes encoding corticotropin releasing hormone receptor 1 (CRHR1), tachykinin receptor 1 (TACR1), gastrin releasing peptide (GRP), and gastrin releasing peptide receptor (GRPR) were selected as candidates for PD based on their biology. Linkage and association analysis in 120 multiplex U.S. PD pedigrees was performed using 21 single nucleotide polymorphisms (SNPs). Parametric and non-parametric linkage tests in pedigrees, for single point and multipoint analysis, revealed limited support for genetic linkage to TACR1 (parametric and non-parametric lod scores ∼1). The family-based association test (FBAT) generated nominal support for allelic association in TACR1 (P = 0.02), and GRP (P = 0.02), findings which must be considered in the light of multiple comparisons. Further exploration of the GRP and TACR1 findings in large case-control PD samples may provide more definitive evidence implicating these loci in the genetic etiology of PD. © 2008 Wiley-Liss, Inc.

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