Intermediate phenotype analysis of patients, unaffected siblings, and healthy controls identifies VMAT2 as a candidate gene for psychotic disorder and neurocognition

C.J. Simons, R. van Winkel, R. Bruggeman, W. Cahn, L. de Haan, R.S. Kahn, L. Krabbendam, D. Linzen, I. Myin-Germeys, J van Os, D. Wiersma

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    Psychotic disorders are associated with neurocognitive alterations that aggregate in unaffected family members, suggesting that genetic vulnerability to psychotic disorder impacts neurocognition. The aim of the present study was to investigate whether selected schizophrenia candidate single nucleotide polymorphisms (SNPs) are associated with (1) neurocognitive functioning across populations at different genetic risk for psychosis (2) and psychotic disorder. The association between 152 SNPs in 43 candidate genes and a composite measure of neurocognitive functioning was examined in 718 patients with psychotic disorder. Follow-up analyses were carried out in 750 unaffected siblings and 389 healthy comparison subjects. In the patients, 13 associations between SNPs and cognitive functioning were significant at P <. 05, situated in DRD1, DRD3, SLC6A3, BDNF, FGF2, SLC18A2, FKBP5, and DNMT3B. Follow-up of these SNPs revealed a significant and directionally similar association for SLC18A2 (alternatively VMAT2) rs363227 in siblings (B = -0.13, P =. 04) and a trend association in control subjects (B = -0.10, P =. 12). This association was accompanied by a significantly increased risk for psychotic disorder associated with the T allele (linear OR = 1.51, 95% CI 1.10-2.07, P =. 01), which was reduced when covarying for cognitive performance (OR = 1.29, 95% CI 0.92-1.81, P =. 14), suggesting mediation. Genetic variation in VMAT2 may be linked to alterations in cognitive functioning underlying psychotic disorder, possibly through altered transport of monoamines into synaptic vesicles. © The Author 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
    Original languageEnglish
    Pages (from-to)848-56
    JournalSchizophrenia Bulletin
    Volume39
    Issue number4
    Early online date24 Apr 2012
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Dive into the research topics of 'Intermediate phenotype analysis of patients, unaffected siblings, and healthy controls identifies VMAT2 as a candidate gene for psychotic disorder and neurocognition'. Together they form a unique fingerprint.

    Cite this