Cross-Disorder Analysis of Bipolar Risk Genes: Further Evidence of DGKH as a Risk Gene for Bipolar Disorder, but also Unipolar Depression and Adult ADHD

Recently, several genome-wide association studies (GWAS) on bipolar disorder (BPD) suggested novel risk genes. However, only few of them were followed up and further, the specificity of these genes is even more elusive. To address these issues, we genotyped SNPs in ANK3, CACNA1C, CMTM8, DGKH, EGFR,...

Full description

Saved in:
Bibliographic Details
Published in:Neuropsychopharmacology 2011-09, Vol.36 (10), p.2076-2085
Main Authors: WEBER, Heike, KITTEL-SCHNEIDER, Sarah, BAUNE, Bernhard T, GROSS-LESCH, Silke, KOPF, Juliane, KREIKER, Susanne, TRANG NGUYEN, Thuy, WEISSFLOG, Lena, AROLT, Volker, MORS, Ole, DECKERT, Jürgen, LESCH, Klaus-Peter, GESSNER, Alexandra, REIF, Andreas, DOMSCHKE, Katharina, NEUNER, Maria, JACOB, Christian P, BUTTENSCHON, Henriette N, BOREATTI-HÜMMER, Andrea, VOLKERT, Julia, HERTERICH, Sabine
Format: Article
Language:English
Subjects:
Adult
Adult and adolescent clinical studies
Aged
Attention Deficit Disorder with Hyperactivity - enzymology
Attention Deficit Disorder with Hyperactivity - genetics
Attention Deficit Disorder with Hyperactivity - psychology
Attention deficit hyperactivity disorder
Biological and medical sciences
Bipolar disorder
Bipolar Disorder - genetics
Bipolar Disorder - psychology
Bipolar disorders
Depression
Depressive Disorder - genetics
Depressive Disorder - psychology
Diacylglycerol Kinase - genetics
Female
Genes
Genetic Predisposition to Disease - genetics
Genetic Variation - genetics
Genome-Wide Association Study - methods
Genomes
Haplotypes
Humans
Kinases
Male
Medical sciences
Middle Aged
Mood disorders
Neurobiology
Neurosciences
Original
Polymorphism, Single Nucleotide - genetics
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychotherapy
Risk Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Recently, several genome-wide association studies (GWAS) on bipolar disorder (BPD) suggested novel risk genes. However, only few of them were followed up and further, the specificity of these genes is even more elusive. To address these issues, we genotyped SNPs in ANK3, CACNA1C, CMTM8, DGKH, EGFR, and NPAS3, which were significantly associated with BPD in previous GWAS, in a sample of 380 BPD patients. Replicated SNPs were then followed up in patients suffering from unipolar depression (UPD; n=387) or adult attention-deficit/hyperactivity disorder (aADHD; n=535). While we could not confirm an association of ANK3, CACNA1C, and EGFR with BPD, 10 SNPs in DGKH, CMTM8, and NPAS3 were nominally associated with disease, with two DGKH markers surviving correction for multiple testing. When these were followed up in UPD and aADHD, seven DGKH SNPs were also associated with UPD, while one SNP each in NPAS3 and CMTM8 and four in DGKH were linked to aADHD. Furthermore, a DGKH haplotype consisting of rs994856/rs9525580/rs9525584 GAT was associated with all disorders tested, while the complementary AGC haplotype was protective. The corresponding haploblock spans a 27-kb region covering exons coding for amino acids 65-243, and thus might include functional variants yet to be identified. We demonstrate an association of DGKH with BPD, UPD, and aADHD by applying a two-stage design. These disorders share the feature of mood instability, so that this phenotype might be associated with genetic variation in DGKH.
ISSN:0893-133X
1740-634X
0007-0920
DOI:10.1038/npp.2011.98