A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder
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The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 single-nucleotide polymorphisms (SNPs) in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA, and selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost saving and gain in efficiency. A total of 88 SNPs, representing 80 different genes, met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of diacylglycerol kinase eta (DGKH; P=1.5 x 10(-8), experiment-wide P<0.01, OR=1.59). This gene encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease.
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DGKH has been identified as the gene most strongly associated with bipolar disorder.
“Finally, DAG kinase-η (DGKH) has been identified as the gene that is most strongly associated with bipolar disorder138.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [138]
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- Authors
- Baum, A. E., Akula, N., Cabanero, M., Cardona, I., Corona, W., Klemens, B., Schulze, T. G., Cichon, S., Rietschel, M., Nöthen, M. M., Georgi, A., Schumacher, J., Schwarz, M., Abou Jamra, R., Höfels, S., Propping, P., Satagopan, J., Detera-Wadleigh, S. D., Hardy, J., McMahon, F. J., & NIMH Genetics Initiative Bipolar Disorder Consortium
- Affiliations
- National Institutes of Health (US)
- Brookings Institution (US)
- Heidelberg University (DE)
- University of Bonn (DE)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- McMahon, F J
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2007-05-08
- Volume
- 13
- Issue
- 2
- Pages
- 197-207
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2527618
- OpenAlex
- W2169728426
- Cited by
- 700
- References
- 1
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 15 · 2023: 9 · 2022: 17 · 2021: 19 · 2020: 23 · 2019: 23 · 2018: 26 · 2017: 25 · 2016: 45 · 2015: 29 · 2014: 42 · 2013: 42 · 2012: 55
- FWCI
- 51.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (5r01gm060457-03)
- National Institute of Mental Health (R01MH059553, Z01MH002810, R01MH059566, R01MH059571, R01MH059545, R01MH060879, R01MH059565, R01MH060870, R01MH059534, R01MH059533, R01MH061675, R01MH059567, R01MH059556, R01MH059586, R01MH059588, R01MH059535, R01MH067257, R01MH059548, R01MH060068, Z01MH002843, R01MH059587, Z01MH002842)
- National Cancer Institute (R01CA098438)
- National Institute of General Medical Sciences (R01 GM60457)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, single nucleotide polymorphisms, genetic susceptibility, polygenic disease, phosphatidylinositol pathway, lithium sensitivity, risk genes
- MeSH terms
- Bipolar Disorder, Europe, Female, Humans, Male, Models, Biological, Random Allocation, Linkage Disequilibrium, Case-Control Studies, Genome, Diacylglycerol Kinase, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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