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. 2022 Apr 5;53(6):2619–2633. doi: 10.1017/S0033291721004554

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© The Author(s) 2022

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.

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Fig. 4. — Context-specific pheWAS associations. (a) Concordance of context-specific experiment-wide significant AN-GReX clinical associations with AN direction of effect. We compared the direction of effect (DoE) for each experiment-wide gene–tissue-pheWAS association with the DoE of that gene–tissue pair for AN from our S-PrediXcan results (online Supplemental Methods). For those phenotypes concordant with AN, this may indicate that genetic regulation of those AN-genes is more similar to individuals with AN in individuals with those clinical outcomes. (b) Schematic of the proportion of concordance of AN-GReX pheWAS associations with AN S-PrediXcan associations. Associations with similar direction of effect to AN (green) identified as ‘concordant’, associations with opposite direction of effect (purple) identified as ‘discordant’. (c) Context-specific associations of AN-GReX with lipid phenotypes of highest recorded, lowest recorded, and mean measures of total cholesterol (mg/dl), HDL cholesterol (mg/dl), and LDL cholesterol (mg/dl). Experiment-wide significant threshold set at p = 0.05(9 phenotypes × 45 tissues) = 1.2 × 10⁻⁴. Tissue-specific threshold set at 0.05/(9 phenotypes) = 0.0056. Context-specific associations of AN-GReX with pain location for (d) experiment-wide significant associations (p = 0.05/(99 phenotypes × 45 tissues) = 1.1 × 10⁻⁵), (e) all context-specific associations (experiment-wide and tissue-specific) with generalized pain, and (f) with foot pain. Tissue-specific threshold for pain location set at 0.05/(99 phenotypes) = 5.0 × 10⁻⁴.