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bioRxiv · 10.1101/2020.09.19.304832

Shared associations identify causal relationships between gene expression and immune cell phenotypes

Gasperi, C.·Chun, S.·Sunyaev, S.·Cotsapas, C.
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Abstract

Genetic mapping studies have identified thousands of associations between common variants and hundreds of human traits. Translating these associations into mechanisms is complicated by two factors: they fall into gene regulatory regions; and they are rarely mapped to one causal variant. One way around these limitations is to find groups of traits that share associations, using this genetic link to infer a biological connection. Here, we assess how many trait associations in the same locus are due to the same genetic variant, and thus shared; and if these shared associations are due to causal relationships between traits. We find that only a subset of traits share associations, with most due to causal relationships rather than pleiotropy. We therefore suggest that simply observing overlapping associations at a genetic locus is insufficient to infer causality; direct evidence of shared associations is required to support mechanistic hypotheses in genetic studies of complex traits.

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Gasperi, C., Chun, S., Sunyaev, S., Cotsapas, C.. 2020-09-20. Shared associations identify causal relationships between gene expression and immune cell phenotypes. https://doi.org/10.1101/2020.09.19.304832

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