ArticleTranslational psychiatry2019
Evidence that genes involved in hedgehog signaling are associated with both bipolar disorder and high BMI.
Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Comprehensive analysis of interactions between brain aging and late-onset psychoses using heuristic mapping models.Communications medicine · 2026Article
- Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health.Molecular psychiatry · 2026Article
- Conserved NT5C2 links context-specific behaviors with psychiatric and metabolic risk.Behavioral and brain functions : BBF · 2026Article
- Genome-wide analysis in over 1.6 million participants uncovers 147 loci associated with obstructive sleep apnoea.medRxiv : the preprint server for health sciences · 2025Article
- Is the Hedgehog Pathway Involved in the Pathophysiology of Schizophrenia? A Systematic Review of Current Evidence of Neural Molecular Correlates and Perspectives on Drug Development.Current issues in molecular biology · 2024Review
- Single-cell genomics and regulatory networks for 388 human brains.Science (New York, N.Y.) · 2024Article
- Appetite hormone dysregulation and executive dysfunction among adolescents with bipolar disorder and disruptive mood dysregulation disorder.European child & adolescent psychiatry · 2024Article
- Single-cell genomics and regulatory networks for 388 human brains.bioRxiv : the preprint server for biology · 2024Article
- Phenotype integration improves power and preserves specificity in biobank-based genetic studies of major depressive disorder.Nature genetics · 2023Article
- Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference.Behavioral neuroscience · 2023Article
- Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study.BMC psychiatry · 2023Article
- Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.Communications biology · 2023Article
- CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor.BMC psychiatry · 2023Article
- Early-Onset Type 2 Diabetes and Mood, Anxiety, and Stress-Related Disorders: A Genetically Informative Register-Based Cohort Study.Diabetes care · 2022Article
- The genetics of bipolar disorder with obesity and type 2 diabetes.Journal of affective disorders · 2022Review
- PTBP2 - a gene with relevance for both Anorexia nervosa and body weight regulation.Translational psychiatry · 2022Article
- Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Genetic Associations with Weight Gain among South Africans who Initiated Dolutegravir-Containing and Tenofovir-Containing Regimens.Journal of acquired immune deficiency syndromes (1999) · 2021Article
- Applying dimensional psychopathology: transdiagnostic associations among regional homogeneity, leptin and depressive symptoms.Translational psychiatry · 2020Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with bipolar disorder (BD) show higher frequency of obesity and type 2 diabetes (T2D), but the underlying genetic determinants and molecular pathways are not well studied. Using large publicly available datasets, we (1) conducted a gene-based analysis using MAGMA to identify genes associated with BD and body mass index (BMI) or T2D and investigated their functional enrichment; and (2) performed two meta-analyses between BD and BMI, as well as BD and T2D using Metasoft. Target druggability was assessed using the Drug Gene Interaction Database (DGIdb). We identified 518 and 390 genes significantly associated with BD and BMI or BD and T2D, respectively. A total of 52 and 12 genes, respectively, were significant after multiple testing correction. Pathway analyses conducted on nominally significant targets showed that genes associated with BD and BMI were enriched for the Neuronal cell body Gene Ontology (GO) term (p = 1.0E-04; false discovery rate (FDR) = 0.025) and different pathways, including the Signaling by Hedgehog pathway (p = 4.8E-05, FDR = 0.02), while genes associated with BD and T2D showed no specific enrichment. The meta-analysis between BD and BMI identified 64 relevant single nucleotide polymorphisms (SNPs). While the majority of these were located in intergenic regions or in a locus on chromosome 16 near and in the NPIPL1 and SH2B1 genes (best SNP: rs4788101, p = 2.1E-24), five were located in the ETV5 gene (best SNP: rs1516725, p = 1E-24), which was previously associated with both BD and obesity, and one in the RPGRIP1L gene (rs1477199, p = 5.7E-09), which was also included in the Signaling by Hedgehog pathway. The meta-analysis between BD and T2D identified six significant SNPs, three of which were located in ALAS1 (best SNP: rs352165, p = 3.4E-08). Thirteen SNPs associated with BD and BMI, and one with BD and T2D, were located in genes which are part of the druggable genome. Our results support the hypothesis of shared genetic determinants between BD and BMI and point to genes involved in Hedgehog signaling as promising targets.
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