Evidence map›Paper›PMID 12140781›Full record

ArticleMolecular psychiatry2002

Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor.

P Sklar, S B Gabriel, M G McInnis, P Bennett, Y -M Lim, G Tsan, S Schaffner, G Kirov, I Jones, M Owen and 3 more

Abstract readMulticenter Study
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 5 pooled it
18.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 5 syntheses or guidelines pooled it, 568 citations in OpenAlex.

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  3. BDNF Val66Met is associated with introversion and interacts with 5-HTTLPR to influence neuroticism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010
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  15. Brain-derived Neurotrophic Factor and High Sensitive C-reactive Protein in Bipolar Depression and Unipolar Depression: The Practical Usage as a Discriminatory Tool.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2023
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  20. Association betweenYonsei medical journal · 2021
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122 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

P SklarDepartment of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. sklar@genome.wi.mit.edu
S B Gabriel
M G McInnis
P Bennett
Y -M Lim
G Tsan
S Schaffner
G Kirov
I Jones
M Owen
N Craddock
J R DePaulo
E S Lander
Whitehead Institute for Biomedical Research · USJohns Hopkins Medicine · USQueen Elizabeth Hospital Birmingham · GBUniversity of Wales · GBMassachusetts General Hospital · USUniversity of Birmingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Identification of the genetic bases for bipolar disorder remains a challenge for the understanding of this disease. Association between 76 candidate genes and bipolar disorder was tested by genotyping 90 single-nucleotide polymorphisms (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit of the voltage-dependent calcium channel were associated with bipolar disorder at the P<0.05 level. In view of the large number of hypotheses tested, the two nominally positive associations were then tested in independent populations of bipolar patients and only BDNF remains a potential risk gene. In the replication samples, excess transmission of the valine allele of amino acid 66 of BDNF was observed in the direction of the original result in an additional sample of 334 parent-proband trios (T/U=108/87, P=0.066). Resequencing of 29 kb surrounding the BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified three additional markers transmitted to bipolar probands at the P < 0.05 level. Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm.

Indexed as

Bipolar DisorderBrain-Derived Neurotrophic FactorChi-Square DistributionFamilyHaplotypesHumansIowaMarylandPolymorphism, Single NucleotideRisk FactorsBrain-Derived Neurotrophic Factor

Identifiers

PMID12140781
OpenAlexW2404639217

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.