Genome wide association studies (GWAS) for behavioral traits and psychiatric disorders have inspired both confident optimism and withering criticism. Although many recent findings from well powered GWAS have been replicated in independent data sets, the genes identified have pinned down few if any underlying causal mechanisms. Therefore, a key issue is whether or not the genes implicated by GWAS form a coherent story on their own and thus could in principle lead to insight into the biological mechanisms underlying the trait or disorder. We sketch here four scenarios for how genes may contribute to traits and disorders; genetic studies may help elucidate mechanisms under only two of our scenarios. We also describe here an approach to characterize, in an unbiased fashion, the molecular coherence of the gene sets implicated by GWAS of various behavioral and psychiatric phenotypes and we sketch how the four scenarios may be reflected in our molecular coherence measure.
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This project was supported by a Genetics and Human Agency Award to KSK. This work is solely the responsibility of the authors and does not necessarily represent the official view of the funders (John Templeton Foundation).
Conflict of interest
Mark A. Reimers, Carl Craver, Mikhail Dozmorov, Silviu-Alin Bacanu and Kenneth S. Kendler declare no conflicts of interest.
This article does not contain any studies with human participants performed by any of the authors.
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Reimers, M.A., Craver, C., Dozmorov, M. et al. The Coherence Problem: Finding Meaning in GWAS Complexity. Behav Genet 49, 187–195 (2019). https://doi.org/10.1007/s10519-018-9935-x
- Psychiatric illness
- Molecular genetics