Evidence map›Paper›PMID 23303482›Full record

ArticleJAMA psychiatry2013

ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.

Elliot C Nelson, Michael T Lynskey, Andrew C Heath, Naomi Wray, Arpana Agrawal, Fiona L Shand, Anjali K Henders, Leanne Wallace, Alexandre A Todorov, Andrew J Schrage and 5 more

Open access · greenAbstract read
In one paragraph

Article in JAMA psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 8 pooled it
7.8field-weighted citation impact, top 3% 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

40 citing papers in PubMed, 8 syntheses or guidelines pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2018
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  12. Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Elliot C NelsonDepartment of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. nelsone@wustl.edu
Michael T Lynskey
Andrew C Heath
Naomi Wray
Arpana Agrawal
Fiona L Shand
Anjali K Henders
Leanne Wallace
Alexandre A Todorov
Andrew J Schrage
Nancy L Saccone
Pamela A F Madden
Louisa Degenhardt
Nicholas G Martin
Grant W Montgomery
Washington University in St. Louis · US

Funding

CANNABIS AND TOBACCO INVOLVEMENT: A TWIN STUDYR01DA023668 · NIDA · WASHINGTON UNIVERSITY · PI AGRAWAL, ARPANA · 2007 to 2016
$2.5M
Opioid Dependence: Candidate Genes and G x E EffectsR01DA017305 · NIDA · WASHINGTON UNIVERSITY · PI NELSON, ELLIOT C · 2003 to 2007
$2.5M
GENE-ENVIRONMENT INTERPLAY IN ALCOHOLISMK05AA017688 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2008 to 2017
$1.9M
NIAAA NIH HHS K05 AA017688NIDA NIH HHS R01 DA017305NIDA NIH HHS R01 DA023668NIDA NIH HHS R01 DA23668
6 · The paper itself

Abstract

contextThe genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging.

objectiveTo examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations.

designCase-control genetic association study that included 2 control groups (lacking an established optimal control group).

settingSemistructured psychiatric interviews.

participantsA total of 1459 Australian cases ascertained from opioid replacement therapy clinics, 531 neighborhood controls ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and 1495 unrelated Australian Twin Registry controls not dependent on alcohol or illicit drugs selected from a twin and family sample.

main outcome measureLifetime heroin dependence.

resultsComparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (P ≥ .01); a similar comparison with neighborhood controls revealed greater differences (P ≥ 1.8 × 10(-4)). Comparing cases (n = 1459) with the subgroup of neighborhood controls not dependent on illicit drugs (n = 340), 3 SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 (most strongly associated; odds ratio = 1.59; 95% CI, 1.32-1.92; P = 9.7 × 10(-7)), ANKK1 SNP rs4938013, and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (n = 191) and nondependent (n = 340) neighborhood controls, suggesting that liability likely extends to nonopioid illicit drug dependence. Aggregate heroin dependence risk associated with 2 SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (P = 2.7 × 10(-9) for the risk-associated linear trend).

conclusionsOur results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence.

Indexed as

AdultAustraliaCase-Control StudiesCD56 AntigenFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHeroin DependenceHumansLogistic ModelsMaleMiddle AgedPolymorphism, Single NucleotideProteinsANKK1 protein, humanCD56 AntigenNCAM1 protein, humanProteinsProtein Serine-Threonine KinasesReceptors, Dopamine D2TTC12 protein, human

Identifiers

PMID23303482
PMCPMC3789525
OpenAlexW2147919295

What OpenQuestion holds

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Registered trials

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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.