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

Laura M. Hodges; Myrna M. Weissman; Fatemeh Haghighi; Ramiro Costa; Oscar Bravo; Oleg Evgrafov; James A. Knowles; Abby J. Fyer; Steven P. Hamilton

doi:10.1002/ajmg.b.30773

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

Laura M. Hodges, Myrna M. Weissman, Fatemeh Haghighi, Ramiro Costa, Oscar Bravo, Oleg Evgrafov, James A. Knowles, Abby J. Fyer, Steven P. Hamilton

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22 Scopus citations

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.

Original language	English
Pages (from-to)	65-73
Number of pages	9
Journal	American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume	150
Issue number	1
DOIs	https://doi.org/10.1002/ajmg.b.30773
State	Published - 5 Jan 2009
Externally published	Yes

Keywords

Corticotropin releasing hormone
Gastrin-releasing peptide
Neuropeptide
SNP
Tachykinin

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

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.",

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author = "Hodges, {Laura M.} and Weissman, {Myrna M.} and Fatemeh Haghighi and Ramiro Costa and Oscar Bravo and Oleg Evgrafov and Knowles, {James A.} and Fyer, {Abby J.} and Hamilton, {Steven P.}",

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AU - Weissman, Myrna M.

AU - Haghighi, Fatemeh

AU - Costa, Ramiro

AU - Bravo, Oscar

AU - Evgrafov, Oleg

AU - Knowles, James A.

AU - Fyer, Abby J.

AU - Hamilton, Steven P.

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N2 - 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.

AB - 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.

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

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Keywords

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