title: The DRD2 rs1076560 polymorphism and schizophrenia-related intermediate phenotypes: A systematic review and meta-analysis.
abstract: Intermediate phenotypes may contribute to elucidate the genetic determinants of schizophrenia. A regulatory dopamine 2-receptor gene (DRD2) polymorphism (rs1076560; G>T) has been identified as a genetic risk factor for schizophrenia. Studies report conflicting results on its involvement in schizophrenia intermediate phenotypes and no systematic review on this topic has been published. Therefore, we aimed to assess whether this polymorphism is implicated in schizophrenia intermediate phenotypes by performing a systematic review and meta-analysis. Alternative allele carrier status negatively affected all intermediate phenotypes except for brain morphology, for which inconsistent genotype effects were found. Specifically, alternative allele carriers showed inefficient brain recruitment in healthy subjects and decreased brain recruitment in schizophrenia patients. Finally, significant results of the meta-analysis on functional magnetic resonance imaging in healthy subjects pinpointed rs1076560-associated brain regions, in particular the fronto-striatal network. To increase homogeneity and thus improve comparability in future genetic studies investigating SCZ intermediate phenotypes, we highlight methodological caveats and provide suggestions to circumvent such pitfalls.
authors.affiliation: Department of Translational Neuroscience, Human Neurogenetics Unit, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands; Department of Psychiatry, ZNA Hospitals, Antwerp, Belgium. Electronic address: j.luykx@umcutrecht.nl.
authors.forename: Jurjen J
authors.initials: JJ
authors.lastname: Luykx
authors.affiliation: Department of Translational Neuroscience, Human Neurogenetics Unit, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Juliette L
authors.initials: JL
authors.lastname: Broersen
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands; Bipolar Disorder Outpatient Clinic, Mental Health Care Rivierduinen, Leiden, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: de Leeuw
mesh_terms: D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2
keywords: DRD2; Functional magnetic resonance imaging (fMRI); Meta-analysis; Schizophrenia; Systematic review; rs1076560