Neurotransmission and Bipolar Disorder: A Systematic Family-based Association Study

Jiajun Shi; Judith A Badner; Eiji Hattori; James B Potash; Virginia L Willour; Francis J McMahon; Elliot S Gershon; Chunyu Liu

doi:10.1002/ajmg.b.30769

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Neurotransmission and Bipolar Disorder: A Systematic Family-based Association Study

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Neurotransmission and Bipolar Disorder: A Systematic Family-based Association Study

Jiajun Shi, Judith A Badner, Eiji Hattori, James B Potash, Virginia L Willour, Francis J McMahon, Elliot S Gershon and Chunyu Liu

American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.147B(7), pp.1270-1277

10/05/2008

DOI: 10.1002/ajmg.b.30769

PMCID: PMC2574701

PMID: 18444252

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https://www.ncbi.nlm.nih.gov/pmc/articles/2574701View

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Abstract

Neurotransmission pathways/systems have been proposed to be involved in the pathophysiology and treatment of bipolar disorder for over forty years. In order to test the hypothesis that common variants of genes in one or more of five neurotransmission systems confer risk for bipolar disorder, we analyzed 1005 tag single nucleotide polymorphisms in 90 genes from dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmitter systems in 101 trios and 203 quads from Caucasian bipolar families. Our sample has 80% power to detect ORs ≥ 1.82 and ≥ 1.57 for minor allele frequencies of 0.1 and 0.5, respectively. Nominally significant allelic and haplotypic associations were found for genes from each neurotransmission system, with several reaching gene-wide significance (allelic:\nGRIA1\n,\nGRIN2D\n, and\nQDPR\n; haplotypic:\nGRIN2C\n,\nQDPR\n, and\nSLC6A3\n). However, none of these associations survived correction for multiple testing in an individual system, or in all systems considered together. Significant single nucleotide polymorphism associations were not found with sub-phenotypes (alcoholism, psychosis, substance abuse, and suicide attempts) or significant gene-gene interactions. These results suggest that, within the detectable odds ratios of this study, common variants of the selected genes in the five neurotransmission systems do not play major roles in influencing the risk for bipolar disorder or comorbid sub-phenotypes.

bipolar disorder

neurotransmitter

single nucleotide polymorphism

amino acid

monoamine

Details

Title: Subtitle: Neurotransmission and Bipolar Disorder: A Systematic Family-based Association Study
Creators: Jiajun Shi - Department of Psychiatry, University of Chicago, Chicago, IL 60637, USA
Judith A Badner - Department of Psychiatry, University of Chicago, Chicago, IL 60637, USA
Eiji Hattori - Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
James B Potash - Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
Virginia L Willour - Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
Francis J McMahon - Genetic Basis of Mood and Anxiety Disorders Unit, Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892, USA
Elliot S Gershon - Department of Psychiatry, University of Chicago, Chicago, IL 60637, USA
Chunyu Liu - Department of Psychiatry, University of Chicago, Chicago, IL 60637, USA
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.147B(7), pp.1270-1277
DOI: 10.1002/ajmg.b.30769
PMID: 18444252
PMCID: PMC2574701
NLM abbreviation: Am J Med Genet B Neuropsychiatr Genet
ISSN: 1552-4841
eISSN: 1552-485X
Language: English
Date published: 10/05/2008
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984070860102771

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