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Fig 1.

Manhattan Plot of association P-values.

95,499 variants were investigated for association with DCM by logistic regression analysis. Associations are summarized in a Manhattan plot (R/qqman package) which displays the eleven SNVs significantly associated with DCM (Q-values < 0.01) as green dots. Note that the applied logistic model assumed an additive mode of inheritance. For variants on chromosome 15 in the ALPK3 region, a dominant mode of inheritance was better supported by the data (see Table 1 for corresponding P-values)

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Fig 1 Expand

Fig 2.

Forest Plots of odd-ratios (log) in the different populations.

The results show that the associations were largely homogeneous across populations (See also heterogeneity column in Table 2)

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Fig 2 Expand

Table 1.

Variants associated with DCM.

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Table 1 Expand

Fig 3.

Regional plots of association at 8 loci.

P-values, obtained from logistic regression analysis of genotyped and imputed variants in genomic regions demonstrating significant association with DCM are depicted. In each region, the genotyped lead-SNV is identified by its position and the other variants are colored to reflect their LD with the lead-SNV.

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Fig 4.

BAG3 interacts with HspB7.

(A) GST Pull-Down showing interaction of GFP-BAG3 expressed in HEK293 cells and recombinant GST-HSPB7. GFP-BAG3 was expressed in HEK293 cells (cell extract panel) and and GST-HSPB7 was produced in a bacterial expression system. GST-HSPB7 co-sediment with GFP-BAG3 but not with GFP alone indicating specific BAG3/GST-HSPB7 interaction (Pull-Down panel). (B) Co-immunoprecipitation experiment showing interaction of Flag-HSPB7 and GFP-BAG3 in HEK293 cells. GFP alone or GFP-BAG3 were co-expressed together with Flag-HSPB7 in HEK293 cells (cell extract panel) and subjected to immunoprecipitation with an antibody against GFP. Only GFP-BAG3 immunoprecipitated with FLAG-HSPB7 (IP:GFP panel). Western blottings in (A) and (B) used HSPB7 (for GST-HSPB7), GFP (for GFP and GFP-BAG3), and α-tubulin specific antibodies.

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Table 2.

Gene-level association analysis of genes identified in the SNP-level analysis

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Table 2 Expand

Table 3.

DCM gene set association analysis

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Table 3 Expand