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

Mònica Gratacòs, Javier Costas, Rafael De Cid, Mònica Bayés, Juan R. González, Enrique Baca-García, Yolanda De Diego, Fernando Fernández-Aranda, José Fernández-Piqueras, Miriam Guitart, Rocío Martín-Santos, Lourdes Martorell, José M. Menchón, Miquel Roca, Jerónimo Sáiz-Ruiz, Julio Sanjuán, Marta Torrens, Mikel Urretavizcaya, Joaquín Valero, Elisabet VilellaXavier Estivill, Ángel Carracedo

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76 Citations (Scopus)

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, andmooddisorders) 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.

Original languageEnglish
Pages (from-to)808-816
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number6
DOIs
Publication statusPublished - 5 Sep 2009

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Keywords

  • Candidate gene
  • Case-control studies
  • Molecular epidemiology
  • SNP

ASJC Scopus subject areas

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

Cite this

Gratacòs, M., Costas, J., De Cid, R., Bayés, M., González, J. R., Baca-García, E., De Diego, Y., Fernández-Aranda, F., Fernández-Piqueras, J., Guitart, M., Martín-Santos, R., Martorell, L., Menchón, J. M., Roca, M., Sáiz-Ruiz, J., Sanjuán, J., Torrens, M., Urretavizcaya, M., Valero, J., ... Carracedo, Á. (2009). 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. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 150(6), 808-816. https://doi.org/10.1002/ajmg.b.30902