Clock Genes may Influence Bipolar Disorder Susceptibility and Dysfunctional Circadian Rhythm

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

doi:10.1002/ajmg.b.30714

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Clock Genes may Influence Bipolar Disorder Susceptibility and Dysfunctional Circadian Rhythm

Journal article

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Clock Genes may Influence Bipolar Disorder Susceptibility and Dysfunctional Circadian Rhythm

Jiajun Shi, Jacqueline K Wittke-Thompson, 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.1047-1055

10/05/2008

DOI: 10.1002/ajmg.b.30714

PMCID: PMC2574897

PMID: 18228528

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https://www.ncbi.nlm.nih.gov/pmc/articles/2574897View

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Abstract

Several previous studies suggest that dysfunction of circadian rhythms may increase susceptibility to bipolar disorder (BP). We conducted an association study of five circadian genes (\nCRY2\n,\nPER1\n-\n3\n, and\nTIMELESS\n) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (\nARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK\n,\nCRY1\n,\nCSNK1D\n,\nCSNK1E\n,\nDBP\n, and\nNR1D1\n) in an extended family collection of 70 trios and 237 quads (Sample II), which includes the same 114 families but not necessarily the same individuals as Sample I. In Sample II, the Sibling-Transmission Disequilibrium Test (sib-tdt) analysis showed nominally significant association of BP with three SNPs within or near the\nCLOCK\ngene (rs534654,\np\n= 0.0097; rs6850524,\np\n= 0.012; rs4340844,\np\n= 0.015). In addition, SNPs in the\nARNTL2\n,\nCLOCK\n,\nDBP\n, and\nTIMELESS\ngenes and haplotypes in the\nARNTL\n,\nCLOCK\n,\nCSNK1E\n, and\nTIMELESS\ngenes showed suggestive evidence of association with several circadian phenotypes identified in BP patients. However, none of these associations reached gene-wide or experiment-wide significance after correction for multiple-testing. A multi-locus interaction between rs6442925 in the 5′ upstream of\nBHLHB2\n, rs1534891 in\nCSNK1E\n, and rs534654 near the 3′ end of the\nCLOCK\ngene, however, is significantly associated with BP (\np\n= 0.00000172). It remains significant after correcting for multiple testing using the False Discovery Rate method. Our results indicate an interaction between three circadian genes in susceptibility to bipolar disorder.

bipolar disorder

haplotype

single nucleotide polymorphism

circadian rhythm

linkage disequilibrium

Details

Title: Subtitle: Clock Genes may Influence Bipolar Disorder Susceptibility and Dysfunctional Circadian Rhythm
Creators: Jiajun Shi - Department of Psychiatry, University of Chicago, Chicago, IL 60637, USA
Jacqueline K Wittke-Thompson - 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 (BSI), 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.1047-1055
DOI: 10.1002/ajmg.b.30714
PMID: 18228528
PMCID: PMC2574897
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: 9984070869902771

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