ArticleArchives of general psychiatry2008
Association study of Wnt signaling pathway genes in bipolar disorder.
Article in Archives of general psychiatry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.Biological psychiatry · 2023Pooled it
- Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism.Journal of human genetics · 2017Pooled it
- BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies.PloS one · 2013Pooled it
- Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy.PM & R : the journal of injury, function, and rehabilitation · 2018Trial
- A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform.The pharmacogenomics journal · 2010Trial
- Metabolic plasticity: an evolutionary perspective on metabolic and circadian dysregulation in bipolar disorder.Molecular psychiatry · 2025Review
- Excess Wnt in neurological disease.The Biochemical journal · 2025Review
- Apically localized PANX1 impacts neuroepithelial expansion in human cerebral organoids.Cell death discovery · 2024Article
- Differential Expression of Proteins Associated with Bipolar Disorder as Identified Using the PeptideShaker Software.International journal of molecular sciences · 2023Article
- The Relationship between rs534654 Polymorphism in TMEM165 Gene and Increased Risk of Bipolar Disorder Type 1.International journal of molecular and cellular medicine · 2021Article
- Translational genomics and beyond in bipolar disorder.Molecular psychiatry · 2021Review
- Variants and expression changes in PPAR-encoding genes display no significant association with schizophrenia.Bioscience reports · 2020Observational
- The genetics of bipolar disorder.Molecular psychiatry · 2020Review
- Modulation of Stem Cells as Therapeutics for Severe Mental Disorders and Cognitive Impairments.Frontiers in psychiatry · 2020Review
- Aberrant mitochondrial function in patient-derived neural cells from CDKL5 deficiency disorder and Rett syndrome.Human molecular genetics · 2019Article
- Wnt/β-catenin signaling in brain development and mental disorders: keeping TCF7L2 in mind.FEBS letters · 2019Review
- PPAR and GST polymorphisms may predict changes in intellectual functioning in medulloblastoma survivors.Journal of neuro-oncology · 2019Article
- Nuclear receptors in neural stem/progenitor cell homeostasis.Cellular and molecular life sciences : CMLS · 2017Review
- Assessment of Whole-Exome Sequence Data in Attempted Suicide within a Bipolar Disorder Cohort.Molecular neuropsychiatry · 2017Article
- Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry.Molecular neuropsychiatry · 2017Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
contextThe Wnt signaling pathways promote cell growth and are best known for their role in embryogenesis and cancer. Several lines of evidence suggest that these pathways might also be involved in bipolar disorder.
objectiveTo test for an association between candidate genes in the Wnt signaling pathways and disease susceptibility in a family-based bipolar disorder study.
designTwo hundred twenty-seven tagging single- nucleotide polymorphisms (SNPs) from 34 genes were successfully genotyped. Initial results led us to focus on the gene PPARD, in which we genotyped an additional 13 SNPs for follow-up.
settingNine academic medical centers in the United States.
participantsFive hundred fifty-four offspring with bipolar disorder and their parents from 317 families.
main outcome measuresFamily-based association using FBAT and HBAT (http://www.biostat.harvard.edu/~fbat/default.html; Harvard School of Public Health, Boston, Massachusetts). Exploratory analyses testing for interactions of PPARD SNPs with clinical covariates and with other Wnt genes were conducted with GENASSOC (Stata Corp, College Station, Texas).
resultsIn the initial analysis, the most significantly associated SNP was rs2267665 in PPARD (nominal P < .001). This remained significant at P = .05 by permutation after accounting for all SNPs tested. Additional genotyping in PPARD yielded 4 SNPs in 1 haplotype block that were significantly associated with bipolar disorder (P < .01), the most significant being rs9462082 (P < .001). Exploratory analyses revealed significant evidence (P < .01) for interactions of rs9462082 with poor functioning on the Global Assessment Scale (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.85-6.08) and with SNPs in WNT2B (rs3790606: OR, 2.56; 95% CI, 1.67-4.00) and WNT7A (rs4685048: OR, 1.79; 95% CI, 1.23-2.63).
conclusionsWe found evidence for association of bipolar disorder with PPARD, a gene in the Wnt signaling pathway. The consistency of this result with one from the Wellcome Trust Case-Control Consortium encourages further study. If the finding can be confirmed in additional samples, it may illuminate a new avenue for understanding the pathogenesis of severe bipolar disorder and developing more effective treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.