TY - JOUR
T1 - Specific and common genes implicated across major mental disorders
T2 - A review of meta-analysis studies
AU - Gatt, Justine M.
AU - Burton, Karen L.O.
AU - Williams, Leanne M.
AU - Schofield, Peter R.
N1 - Funding Information:
This project was supported by an Australian Research Council (ARC)-Linkage Grant (LP0883621) with LMW as chief investigator, PRS as co-investigator, JMG as postdoctoral research fellow and Brain Resource Ltd as industry partner. JMG is currently supported by a NHMRC Career Development Fellowship (APP1062495). Peter R Schofield is supported by an Australian National Health and Medical Research Council (NHMRC) Program Grant 1037196.
Funding Information:
The Brain Resource Ltd. (BR) was the industry partner on the ARC-linkage grant which funded this study, but had no further role in design or implementation of the project. JMG was a postdoctoral fellow on the ARC-linkage grant which funded this project, has previously received consultancy fees from Brain Resource Ltd, and is a stock holder in Freedomsway Corp. Pte. Ltd. LMW is a stock holder in BR, has stock options in BR, has received fees from BR for consultancies unrelated to this study. CLOB and PRS report no potential conflicts of interest.
Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Genotype
KW - GWAS
KW - Mental illness
KW - Meta-analysis
KW - Pleiotrophy
KW - Review
KW - TWIN-E
UR - http://www.scopus.com/inward/record.url?scp=84919385896&partnerID=8YFLogxK
U2 - 10.1016/j.jpsychires.2014.09.014
DO - 10.1016/j.jpsychires.2014.09.014
M3 - Review article
C2 - 25287955
AN - SCOPUS:84919385896
SN - 0022-3956
VL - 60
SP - 1
EP - 13
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -