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The Four Horsemen of the ‘Omicsalypse’: ontology, replicability, probability and epistemology

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Abstract

Much of modern genomics and the other ‘omics’ that tag along, assert that the causal bases of biomedical outcomes are genomically enumerable lists whose effects are predictable with ‘precision’, extensible from samples to all, and enabled by ever-greater hypothesis-free data accumulation. The assertion rests on fundamental, if often implicit assumptions, that (1) the phenomena are based on underlying law-like biological causation, and, therefore, are (2) replicable and (3) even if not deterministic, have specifiable, stable, essentially parametric, probabilities, all of which (4) essentially equates induction with deduction, enabling asymptotically accurate prediction based on past observation. These glowing promises are the four horsemen of a genocentric ‘Omicsalypse’. But what if the assumptions are wrong or appropriate only to an extent that is unknowable, even in principle? Might there be better ways to understand complex traits?

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Acknowledgements

For some of the general issues discussed here, readers may find these discussions useful: (Steup 2018) and (Bard and Rhe 2004). The views expressed here reflect my years of thinking about genetic causation and inference, influenced by many colleagues and students. However, these are my thoughts on current conditions in our science, not a consensus summary; reviewers are not complicit—and perhaps will write their own.

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Correspondence to Kenneth M. Weiss.

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The relevant literature, hundreds of papers per month, would swamp any page limit, and be immediately dated. I only cite a few references that I deem most general and germane.

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Weiss, K.M. The Four Horsemen of the ‘Omicsalypse’: ontology, replicability, probability and epistemology. Hum Genet 139, 115–120 (2020). https://doi.org/10.1007/s00439-019-02007-7

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  • DOI: https://doi.org/10.1007/s00439-019-02007-7

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