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. 2018 Oct 16;9:4285. doi: 10.1038/s41467-018-06540-3

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Pleiotropic effects of IFIH1 LOF variants. a A significant association of IFIH1 rs1990760-C (p.T946A) with increased risk of asthma was observed in the meta-analysis of PheWAS and GWAS results, with consistent effect estimate across the six cohorts tested. Odds ratios (OR) and 95% confidence intervals are represented. b Power estimation demonstrates the lack of power to detect an association at rs1990760-C in currently available asthma GWAS studies. Power to surpass various significance cutoffs (P < 0.05; FDR < 0.1, P < 7e−4; study-wide significance after Bonferroni correction, P < 1.8e−6; and genome-wide significance, P < 5e−8) in the six cohorts was estimated using the frequency of the asthma risk allele (RAF = 0.39), the OR in the PheWAS/GWAS meta-analysis (OR = 1.037), a disease prevalence of 8%, and the number of cases and controls in each of the cohorts. c Co-localization analysis demonstrates that the asthma, systemic lupus erythematosus (SLE), and ulcerative colitis (UC) associations at the IFIH1 locus are driven by a shared causal signal. Regional association results with asthma (red), SLE (blue) and UC (orange) are shown. PP, posterior probability of co-localization. d Results from this study (indicated by an asterix) combined with previously published findings suggest an allelic series of LOF IFIH1 alleles decreasing the risk of various autoimmune diseases while increasing the risk of asthma and UC. OR and 95% confidence intervals of association for the IFIH1 loss-of-function alleles rs1990760-C (p.T946A) and rs35667974-C (p. I923V) are shown