ArticleMolecular psychiatry2006
Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3.
Article in Molecular psychiatry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Pooled it
- The genetics of early-onset bipolar disorder: A systematic review.Journal of affective disorders · 2015Pooled it
- Identification of pathways for bipolar disorder: a meta-analysis.JAMA psychiatry · 2014Pooled it
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness.International journal of molecular sciences · 2023Review
- Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy.International journal of molecular sciences · 2023Review
- TRPM2: bridging calcium and ROS signaling pathways-implications for human diseases.Frontiers in physiology · 2023Review
- TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention.Channels (Austin, Tex.) · 2021Review
- Role of Oxidative Stress and CaFrontiers in cell and developmental biology · 2021Review
- One Single Nucleotide Polymorphism of theDiseases (Basel, Switzerland) · 2020Article
- Roles of TRP Channels in Neurological Diseases.Oxidative medicine and cellular longevity · 2020Review
- Article
- Pharming for Genes in Neurotransmission: Combining Chemical and Genetic Approaches in Caenorhabditis elegans.ACS chemical neuroscience · 2018Review
- TRPM2 in the Brain: Role in Health and Disease.Cells · 2018Review
- Structure of a TRPM2 channel in complex with CaeLife · 2018Article
- TRPM2: a candidate therapeutic target for treating neurological diseases.Acta pharmacologica Sinica · 2018Review
- The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia.Acta pharmacologica Sinica · 2018Review
- A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder.International journal of molecular sciences · 2017Article
- The PHF21B gene is associated with major depression and modulates the stress response.Molecular psychiatry · 2017Article
- Sequencing of sporadic Attention-Deficit Hyperactivity Disorder (ADHD) identifies novel and potentially pathogenic de novo variants and excludes overlap with genes associated with autism spectrum disorder.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Linkage analyses of bipolar families have confirmed that there is a susceptibility locus near the telomere on chromosome 21q. To fine map this locus we carried out tests of allelic association using 30 genetic markers near the telomere at 21q22.3 in 600 bipolar research subjects and 450 ancestrally matched supernormal control subjects. We found significant allelic association with the microsatellite markers D21S171 (P=0.016) and two closely linked single-nucleotide polymorphisms, rs1556314 (P=0.008) and rs1785467 (P=0.025). A test of association with a three locus haplotype across the susceptibility region was significant with a permutation test of P=0.011. A two SNP haplotype was also significantly associated with bipolar disorder (P=0.01). Only two brain expressed genes, TRPM2 and C21ORF29 (TSPEAR), are present in the associated region. TRPM2 encodes a calcium channel receptor and TSPEAR encodes a peptide with repeats associated with epilepsy in the mouse. DNA from subjects who had inherited the associated marker alleles was sequenced. A base pair change (rs1556314) in exon 11 of TRPM2, which caused a change from an aspartic acid to a glutamic acid at peptide position 543 was found. This SNP showed the strongest association with bipolar disorder (P=0.008). Deletion of exon 11 of TRPM2 is known to cause dysregulation of cellular calcium homeostasis in response to oxidative stress. A second nonconservative change from arginine to cysteine at position 755 in TRPM2 (ss48297761) was also detected. A third nonconservative change from histidine to glutamic acid was found in exon 8 of TSPEAR. These changes need further investigation to establish any aetiological role in bipolar disorder.
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