Science Fictions Episode 99.5: Candidate genes
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Apr 21, 2026 A look at why decades of research chased single genes for complex traits and how that idea took hold. Stories about high-profile gene claims like serotonin and MAOA and the media frenzy they sparked. How replication failures, publication bias and underpowered studies overturned many influential findings. The rise of large-scale genetics and why most traits turn out to be highly polygenic.
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MAOA Story Became Media And Court Sensation
- The MAOA 'warrior gene' story began with a Dutch family showing violent behavior and a low-activity MAOA variant linked to antisocial outcomes in Caspi et al. 2002.
- Media and courts sensationalized it, with reduced sentences and cultural claims about Maori populations.
Replication Gap Revealed Systemic Bias
- Replication rates exposed major problems: 96% of novel candidate-GxE studies reported positives versus 27% of replications.
- This mismatch indicates publication bias, low power, and a high false discovery rate in the field.
GWAS Showed Traits Are Massively Polygenic
- GWAS changed expectations by showing most traits are massively polygenic with tiny individual effects.
- Candidate studies' small samples (median ~345) were orders of magnitude underpowered compared with needed sample sizes (~34,000).