ArticleNeuron2016
Genetic Background Limits Generalizability of Genotype-Phenotype Relationships.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 4 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.
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Who cites it
151 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Effects of excess sodium consumption on arterial function in C57BL/6 mice.American journal of physiology. Heart and circulatory physiology · 2024Pooled it
- Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies.PLoS genetics · 2022Pooled it
- Genetic Variants Associated With Resilience in Human and Animal Studies.Frontiers in psychiatry · 2022Pooled it
- Independent evolution toward larger body size in the distinctive Faroe Island mice.G3 (Bethesda, Md.) · 2021Pooled it
- Single-cell RNA sequencing and cross-species analysis revealed the role of T cell-driven inflammatory responses in the pathogenesis of aortic dissection.BMC cardiovascular disorders · 2026Article
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.Genes, brain, and behavior · 2026Article
- Functional impact of genetic background on variable expressivity in neurodevelopmental disorders.Nature communications · 2026Article
- Data-driven prioritization of mouse strains for improved preclinical modeling of rare and common disease.bioRxiv : the preprint server for biology · 2026Article
- DSS Colitis Model: Traps, Tricks, and Reporting Recommendations.Biomedicines · 2026Review
- Beyond Mendel: a call to revisit the genotype-phenotype map through new experimental paradigms.Genetics · 2026Article
- Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.Nature neuroscience · 2026Article
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.bioRxiv : the preprint server for biology · 2026Article
- Thermoregulatory adaptations to cold in C3H/HeJ mice are independent of ADRB3 signaling.Scientific reports · 2026Article
- Inbred C57BL/6J and C57BL/6N mice exhibit differential vascular dysfunction compared with outbred UM-HET3 mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Development of a split-toxin CRISPR screening platform to systematically identify regulators of human myoblast fusion.Nature communications · 2026Article
- Substrain-specific behavioral variation in female C57BL/6 and C57BL/10 mice.Frontiers in behavioral neuroscience · 2026Article
- A mouse organoid platform for modeling cerebral cortex development and cis-regulatory evolution in vitro.Developmental cell · 2025Article
- Organoid: a promising solution to current challenges in cancer immunotherapy.npj biomedical innovations · 2025Review
- Extreme QTL mapping enables the identification of novel zinc toxicity response loci in Drosophila melanogaster.Genetics · 2025Article
- Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Genome-wide association studies (GWASs) have identified numerous loci that influence risk for psychiatric diseases. Genetically engineered mice are often used to characterize genes implicated by GWASs. These studies are based on the assumption that observed genotype-phenotype relationships will generalize to humans, implying that the results would at least generalize to other inbred mouse strains. Given current concerns about reproducibility, we sought to directly test this assumption. We produced F1 crosses between male C57BL/6J mice heterozygous for null alleles of Cacna1c and Tcf7l2 and wild-type females from 30 inbred laboratory strains. We found extremely strong interactions with genetic background that sometimes supported diametrically opposing conclusions. These results do not negate the invaluable contributions of mouse genetics to biomedical science, but they do show that genotype-phenotype relationships cannot be reliably inferred by studying a single genetic background, and thus constitute a major challenge to the status quo. VIDEO ABSTRACT.
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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.