Examination of the clock gene cryptochrome 1 in bipolar disorder: mutational analysis and absence of evidence for linkage or association
Abstract
Bipolar disorder is associated with malfunctions of the circadian system, which regulates individual circadian rhythms and which enables the adaptation to a daily 24-h cycle and seasonal change. One of the human circadian clock genes, cryptochrome 1 (Cry1) (located on 12q23-q24.1) was analyzed because of its close correspondence to a linkage hotspot for bipolar disorder. We found no evidence for linkage of 52 bipolar families to two Cry1 flanking microsatellites under several parametric and non-parametric models. In order to employ association for a more sensitive test, 25 affected subjects selected from families with positive LOD scores were screened for mutations by sequencing 9.5% of the Cry1 gene. A total of 16 single nucleotide polymorphisms (SNPs) and a 3 base pair insertion were identified. However, no mutations with probable functional impact were found. These novel SNPs and data on allele frequency and linkage disequilibrium structure will be useful for future association analyses. Nine SNPs have been analyzed in a set of 159 parent proband triads. Linkage disequilibrium analyses using single SNPs and haplotypes showed no association to bipolar disease.Additional, more powerful, studies involving Cry1 and other circadian clock genes need to be tested before an association of circadian abnormalities with bipolar disorder can be excluded.
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Other studies that examined SNPs throughout the sequence of some central members of the circadian clock have found no associations with these genes and any psychiatric disorders.
“other studies that have examined SNPs throughout the sequence of some of the central members of the circadian clock have found no associations with these genes and any psychiatric disorders (Shiino et al., 2003; Nievergelt et al., 2005; Mansour et al., 2006; Nievergelt et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Nievergelt et al., 2005
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- Authors
- Nievergelt, C. M., Kripke, D. F., Remick, R. A., Sadovnick, A. D., McElroy, S. L., Keck, P. E., & Kelsoe, J. R.
- Affiliations
- University of California San Diego (US)
- St. Paul's Hospital (CA)
- University of British Columbia (CA)
- University of Cincinnati (US)
- Corresponding author
- Kelsoe, John R.
- Venue
- Psychiatric Genetics
- Published
- 2005-03
- Volume
- 15
- Issue
- 1
- Pages
- 45-52
- ISSN
- 0955-8829 (ISSN-L)
- OpenAlex
- W2093383572
- Cited by
- 38
- References
- 56
- Citations by year
- 2023: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29mh047612-05)
- National Institute on Aging (AG 15763, R01AG012364, AG-12364, R01AG015763)
- National Heart, Lung, and Blood Institute (HL61280, R01HL061280)
- National Institute of Mental Health (MH-47612, MH-59567, R01MH059567)
- National Center for Research Resources (M-01RR00827, M01RR000827)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- bipolar disorder, CRY1, clock genes, circadian rhythm, genetic linkage, genetic association, single nucleotide polymorphisms, insertion polymorphism, linkage disequilibrium, haplotypes
- MeSH terms
- Base Sequence, Biological Clocks, Bipolar Disorder, Chromosome Mapping, Chromosomes, Human, Pair 12, DNA Mutational Analysis, Flavoproteins, Gene Frequency, Genotype, Humans, Lod Score, Risk, Linkage Disequilibrium, Polymerase Chain Reaction, DNA Primers, Microsatellite Repeats, Polymorphism, Single Nucleotide, Cryptochromes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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