Evidence map›Paper›PMID 21890791›Full record

ReviewThe American journal of psychiatry2011

A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry.

Laramie E Duncan, Matthew C Keller

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The American journal of psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 461 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
461citing papers in PubMed, 12 pooled it
–field-weighted citation impact
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

461 citing papers in PubMed, 12 syntheses or guidelines pooled it.

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401 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Laramie E DuncanHarvard School of Public Health, Massachusetts General Hospital, McLean Hospital, Harvard Medical School, Belmont, USA. laramied@gmail.com
Matthew C Keller

Funding

RESEARCH TRAINING: DEVELOPMENTAL BEHAVIORAL GENETICST32HD007289 · NICHD · UNIVERSITY OF COLORADO AT BOULDER · PI STALLINGS, MICHAEL CRAIG · 1985 to 2014
$3.1M
Evolutionary Roles of Homozygosity & Copy Number Variation in Mental DisordersK01MH085812 · NIMH · UNIVERSITY OF COLORADO · PI KELLER, MATTHEW CHARLES · 2010 to 2014
$751k
NICHD NIH HHS T32 HD007289NIMH NIH HHS K01 MH085812NIMH NIH HHS MH085812
6 · The paper itself

Abstract

objectiveGene-by-environment interaction (G×E) studies in psychiatry have typically been conducted using a candidate G×E (cG×E) approach, analogous to the candidate gene association approach used to test genetic main effects. Such cG×E research has received widespread attention and acclaim, yet cG×E findings remain controversial. The authors examined whether the many positive cG×E findings reported in the psychiatric literature were robust or if, in aggregate, cG×E findings were consistent with the existence of publication bias, low statistical power, and a high false discovery rate.

methodThe authors conducted analyses on data extracted from all published studies (103 studies) from the first decade (2000-2009) of cG×E research in psychiatry.

resultsNinety-six percent of novel cG×E studies were significant compared with 27% of replication attempts. These findings are consistent with the existence of publication bias among novel cG×E studies, making cG×E hypotheses appear more robust than they actually are. There also appears to be publication bias among replication attempts because positive replication attempts had smaller average sample sizes than negative ones. Power calculations using observed sample sizes suggest that cG×E studies are underpowered. Low power along with the likely low prior probability of a given cG×E hypothesis being true suggests that most or even all positive cG×E findings represent type I errors.

conclusionsIn this new era of big data and small effects, a recalibration of views about groundbreaking findings is necessary. Well-powered direct replications deserve more attention than novel cG×E findings and indirect replications.

Indexed as

EnvironmentGenetic Predisposition to DiseaseHumansMental DisordersPsychiatry

Identifiers

PMID21890791
PMCPMC3222234

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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.