Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Candidate gene studies of a promising intermediate phenotype: failure to replicate.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Trans-ancestry meta-analysis of genome wide association studies of inhibitory control.Molecular psychiatry · 2023Pooled it
- Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.Behavior genetics · 2016Pooled it
- Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment.Addiction biology · 2024Trial
- No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA.European journal of clinical pharmacology · 2018Trial
- Serotonin and Dopamine Gene Variation and Theory of Mind Decoding Accuracy in Major Depression: A Preliminary Investigation.PloS one · 2016Trial
- Differences in subjective response to alcohol in heavy- and light-drinking Chinese men versus Caucasian American men.Addiction (Abingdon, England) · 2015Trial
- Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder.Journal of child and adolescent psychopharmacology · 2014Trial
- Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A rapid review of genetic association studies of parent-of-origin effects and fetal growth.Molecular and cellular pediatrics · 2026Review
- Cocaine-Induced Changes in the BRD4 Interactome Identifies Casein Kinase 1 Epsilon as a Therapeutic Target.Journal of neurochemistry · 2026Article
- Genetic Associations of Persistent Opioid Use After Surgery Point to OPRM1 but Not Other Opioid-Related Loci as the Main Driver of Opioid Use Disorder.Genetic epidemiology · 2025Article
- Genotype-by-diagnosis interaction influences self-control in human cocaine addiction.Translational psychiatry · 2023Article
- The role of the SLC6A3 3' UTR VNTR in nicotine effects on cognitive, affective, and motor function.Psychopharmacology · 2022Article
- Toward Precision Medicine in ADHD.Frontiers in behavioral neuroscience · 2022Review
- Individual Differences in Intertemporal Choice.Frontiers in psychology · 2021Review
- The Association of Aquaporin-1 Gene with Marathon Running Performance Level: a Confirmatory Study Conducted in Male Hispanic Marathon Runners.Sports medicine - open · 2020Article
- Linking Delay Discounting and Substance Use Disorders: Genotypes and Phenotypes.Perspectives on behavior science · 2019Article
- Genomic basis of delayed reward discounting.Behavioural processes · 2019Review
- Weak effects of common genetic variation in oxytocin and vasopressin receptor genes on rhesus macaque social behavior.American journal of primatology · 2018Article
- Self-reported Smoking Status, TAS2R38 Variants, and Propylthiouracil Phenotype: An Exploratory Crowdsourced Cohort Study.Chemical senses · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Many candidate gene studies use 'intermediate phenotypes' instead of disease diagnoses. It has been proposed that intermediate phenotypes have simpler genetic architectures such that individual alleles account for a larger percentage of trait variance. This implies that smaller samples can be used to identify genetic associations. Pharmacogenomic drug challenge studies may be an especially promising class of intermediate phenotype. We previously conducted a series of 12 candidate gene analyses of acute subjective and physiological responses to amphetamine in 99-162 healthy human volunteers (ADORA2A, SLC6A3, BDNF, SLC6A4, CSNK1E, SLC6A2, DRD2, FAAH, COMT, OPRM1). Here, we report our attempt to replicate these findings in over 200 additional participants ascertained using identical methodology. We were unable to replicate any of our previous findings. These results raise critical issues related to non-replication of candidate gene studies, such as power, sample size, multiple testing within and between studies, publication bias and the expectation that true allelic effect sizes are similar to those reported in genome-wide association studies. Many of these factors may have contributed to our failure to replicate our previous findings. Our results should instill caution in those considering similarly designed studies.
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Registered trials
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.