title: Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
abstract: A fundamental difficulty in human genetics research is the identification of the spectrum of genetic variants that contribute to the susceptibility to common/complex disorders. We tested here the hypothesis that functional genetic variants may confer susceptibility to several related common disorders. We analyzed five main psychiatric diagnostic categories (substance-abuse, anxiety, eating, psychotic, and mood disorders) and two different control groups, representing a total of 3,214 samples, for 748 promoter and non-synonymous single nucleotide polymorphisms (SNPs) at 306 genes involved in neurotransmission and/or neurodevelopment. We identified strong associations to individual disorders, such as growth hormone releasing hormone (GHRH) with anxiety disorders, prolactin regulatory element (PREB) with eating disorders, ionotropic kainate glutamate receptor 5 (GRIK5) with bipolar disorder and several SNPs associated to several disorders, that may represent individual and related disease susceptibility factors. Remarkably, a functional SNP, rs945032, located in the promoter region of the bradykinin receptor B2 gene (BDKRB2) was associated to three disorders (panic disorder, substance abuse, and bipolar disorder), and two additional BDKRB2 SNPs to obsessive-compulsive disorder and major depression, providing evidence for common variants of susceptibility to several related psychiatric disorders. The association of BDKRB2 (odd ratios between 1.65 and 3.06) to several psychiatric disorders supports the view that a common genetic variant could confer susceptibility to clinically related phenotypes, and defines a new functional hint in the pathophysiology of psychiatric diseases.
authors.affiliation: CIBER en Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Javier
authors.initials: J
authors.lastname: Costas
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Mònica
authors.initials: M
authors.lastname: Bayés
authors.forename: Juan R
authors.initials: JR
authors.lastname: González
authors.forename: Enrique
authors.initials: E
authors.lastname: Baca-García
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Diego
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.forename: José
authors.initials: J
authors.lastname: Fernández-Piqueras
authors.forename: Miriam
authors.initials: M
authors.lastname: Guitart
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
authors.forename: Lourdes
authors.initials: L
authors.lastname: Martorell
authors.forename: José M
authors.initials: JM
authors.lastname: Menchón
authors.forename: Miquel
authors.initials: M
authors.lastname: Roca
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Sáiz-Ruiz
authors.forename: Julio
authors.initials: J
authors.lastname: Sanjuán
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.forename: Mikel
authors.initials: M
authors.lastname: Urretavizcaya
authors.forename: Joaquín
authors.initials: J
authors.lastname: Valero
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
mesh_terms: D016022:Case-Control Studies; D005796:Genes; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000503:physiopathology; D017720:Molecular Epidemiology; D055495:Neurogenesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D043782:Receptor, Bradykinin B2