Predicting mechanisms of action at genetic loci associated with discordant effects on type 2 diabetes and abdominal fat accumulation
- Department of Biomedical Engineering, University of Virginia, United States
- Center for Public Health Genomics, University of Virginia, United States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, United States
- Department of Medicine, Karolinska Institutet, Huddinge, Sweden
Figures
Figure 1
Analysis summary and discordant variant characteristics.
(A) Summary of analysis pipeline and generated results. Details of data sources are available in Supplementary file 1. (B) Effect size (WHRadjBMI) and odds ratio (T2DadjBMI) of lead genetic variant …
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Figure 1—source data 1
Genetic, transcriptomic, and epigenomic data sources in Figure 1.
- https://cdn.elifesciences.org/articles/79834/elife-79834-fig1-data1-v1.xlsx
Figure 2
Predicting functional tissues and effector genes at discordant loci.
(A) Tissue-specific enrichment of chromatin states of variants in the 99% credible set of colocalized variants. (B) Tissue of action scores for association signals in the five discordant loci. …
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Figure 2—source data 1
Genetic, transcriptomic, and epigenomic data sources used in Figure 2.
- https://cdn.elifesciences.org/articles/79834/elife-79834-fig2-data1-v1.xlsx
Figure 3
Predicted physiological and cellular effects of effector genes (eGenes) on metabolic phenotypes and adipogenesis.
(A) Biweight midcorrelation of adipose tissue eGenes expression with metabolic phenotypes (false discovery rate [FDR] <5%). From left to right: Homeostatic model assessment of insulin resistance …
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Figure 3—source data 1
Genetic, transcriptomic, and epigenomic data sources in Figure 3.
- https://cdn.elifesciences.org/articles/79834/elife-79834-fig3-data1-v1.xlsx
Figure 4 with 2 supplements
Predicted model of effects associated with T allele at rs6860588.
(A) β of the T allele of discordant variant rs6860588 with respect to waist-to-hip circumference adjusted for the body mass index (WHRadjBMI), T2DadjBMI, and colocalized effector genes (eGenes). (B) …
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Figure 4—source data 1
Genetic, transcriptomic, and epigenomic data sources in Figure 4 and Figure 4—figure supplements 1 and 2 .
- https://cdn.elifesciences.org/articles/79834/elife-79834-fig4-data1-v1.xlsx
Figure 4—figure supplement 1
Discordant variant rs6860588 is associated with pleiotropic effects on gene regulation in multiple tissues.
Manhattan plot of associations at the 5q21.1 locus containing lead variant rs6860588 for (A) waist-to-hip circumference adjusted for the body mass index (WHRadjBMI) genome-wide association studies …
Figure 4—figure supplement 2
Discordant variant rs6752964 is associated with pleiotropic effects on gene regulation in multiple tissues.
LocusCompare plot of associations with rs6752964 for (A) waist-to-hip circumference adjusted for the body mass index (WHRadjBMI) genome-wide association studies (GWAS) with T2DadjBMI GWAS, (B) …
Additional files
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Supplementary file 1
Credible set of genetic variants in T2DadjBMI and WHRadjBMI colocalized loci.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp1-v1.xlsx
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Supplementary file 2
Finemapping analysis of association signals in loci containing discordant association signals.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp2-v1.xlsx
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Supplementary file 3
Multi-trait colocalization of body fat distribution component traits in discordant loci.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp3-v1.xlsx
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Supplementary file 4
Variant effect predictions of discordant variants.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp4-v1.xlsx
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Supplementary file 5
Tissue of action scores at colocalized loci.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp5-v1.xlsx
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Supplementary file 6
Significant eQTL and sQTL colocalization results in coloc.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp6-v1.xlsx
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Supplementary file 7
Significant eQTL and sQTL colocalization results in SMR.
- https://cdn.elifesciences.org/articles/79834/elife-79834-supp7-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/79834/elife-79834-mdarchecklist1-v1.pdf
