Examination of the clock gene Cryptochrome 1 in bipolar disorder: mutational analysis and absence of evidence for linkage or association
Bibliographic record
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".