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Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder

2001· article· en· W2151219788 on OpenAlexaff
Tiffany A. Greenwood, Meghan Alexander, Paul E. Keck, Susan L. McElroy, A. Dessa Sadovnick, Ronald A. Remick, John R. Kelsoe

Bibliographic record

VenueAmerican Journal of Medical Genetics · 2001
Typearticle
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsSt. Paul's HospitalUniversity of British Columbia
FundersNational Center for Research ResourcesNational Institute of Mental HealthNational Institute of General Medical SciencesNIH Clinical CenterNational Cancer InstituteUniversity of California, San DiegoU.S. Department of Veterans Affairs
KeywordsLinkage disequilibriumTransmission disequilibrium testGeneticsSingle-nucleotide polymorphismHaplotypeBiologyBipolar disorderLocus (genetics)Genetic linkageAlleleGenotypeGeneEndocrinologyLithium (medication)

Abstract

fetched live from OpenAlex

A role for the dopamine transporter (DAT) in bipolar disorder is implicated by several lines of pharmacological evidence, as well as suggestive evidence of linkage at this locus, which we have reported previously. In an attempt to identify functional mutations within DAT contributing a susceptibility to bipolar disorder, we have screened the entire coding region, as well as significant portions of the adjacent non-coding sequence. Though we have not found a definitive functional mutation, we have identified a number of single nucleotide polymorphisms (SNPs) that span the gene from the distal promoter through exon 15. Of the 39 SNPs that are suitable for linkage disequilibrium (LD) studies, 14 have been analyzed by allele-specific PCR in a sample of 50 parent-proband triads with bipolar disorder. A haplotyped marker comprised of five SNPs, spanning the region between exon 9 and exon 15, was constructed for each individual, and transmission/disequilibrium test (TDT) analysis revealed this haplotype to be in linkage disequilibrium with bipolar disorder (allele-wise TDT p = 0.001, genotype-wise TDT p = 0.0004). These data replicate our previous finding of linkage to markers within and near DAT in a largely different family set, and provide further evidence for a role of DAT in bipolar disorder. Published 2001 Wiley-Liss. Inc.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.439
Threshold uncertainty score0.320

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.038
GPT teacher head0.329
Teacher spread0.291 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations145
Published2001
Admission routes1
Has abstractyes

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