title: Specific and common genes implicated across major mental disorders: a review of meta-analysis studies.
abstract: Major efforts have been directed at family-based association and case-control studies to identify the involvement of candidate genes in the major disorders of mental health. What remains unknown is whether candidate genes are associated with multiple disorders via pleiotropic mechanisms, and/or if other genes are specific to susceptibility for individual disorders. Here we undertook a review of genes that have been identified in prior meta-analyses examining specific genes and specific mental disorders that have core disruptions to emotional and cognitive function and contribute most to burden of illness- major depressive disorder (MDD), anxiety disorders (AD, including panic disorder and obsessive compulsive disorder), schizophrenia (SZ) and bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD). A literature review was conducted up to end-March 2013 which included a total of 1519 meta-analyses across 157 studies reporting multiple genes implicated in one or more of the five disorders studied. A total of 134 genes (206 variants) were identified as significantly associated risk variants for MDD, AD, ADHD, SZ or BD. Null genetic effects were also reported for 195 genes (426 variants). 13 genetic variants were shared in common between two or more disorders (APOE e4, ACE Ins/Del, BDNF Val66Met, COMT Val158Met, DAOA G72/G30 rs3918342, DAT1 40-bp, DRD4 48-bp, SLC6A4 5-HTTLPR, HTR1A C1019G, MTHR C677T, MTHR A1298C, SLC6A4 VNTR and TPH1 218A/C) demonstrating evidence for pleiotrophy. Another 12 meta-analyses of GWAS studies of the same disorders were identified, with no overlap in genetic variants reported. This review highlights the progress that is being made in identifying shared and unique genetic mechanisms that contribute to the risk of developing several major psychiatric disorders, and identifies further steps for progress.
authors.affiliation: The Brain Dynamics Centre, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia; Westmead Millennium Institute, Westmead, NSW, 2145, Australia; Neuroscience Research Australia, Randwick, NSW, 2031, Australia; School of Psychology, University of New South Wales, Sydney, NSW, 2052, Australia. Electronic address: j.gatt@neura.edu.au.
authors.forename: Justine M
authors.initials: JM
authors.lastname: Gatt
authors.affiliation: The Brain Dynamics Centre, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia; Westmead Millennium Institute, Westmead, NSW, 2145, Australia; Neuroscience Research Australia, Randwick, NSW, 2031, Australia; School of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Karen L O
authors.initials: KL
authors.lastname: Burton
authors.affiliation: The Brain Dynamics Centre, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia; Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford University, Stanford, CA, 94305-5717, USA.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
authors.affiliation: Neuroscience Research Australia, Randwick, NSW, 2031, Australia; School of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: GWAS; Genotype; Mental illness; Meta-analysis; Pleiotrophy; Review; TWIN-E