Multi-Organ Physiologic Deficits During Exercise Identify Clinical and Molecular Predisposition to Heart Failure with Preserved Ejection Fraction.

Of note, despite a dramatically smaller sample size in the HFpEF sample in the largest GWAS of HF to date, 41 we found highly significant (Spearman) correlations in gene-level (TWAS) effect size between HF and HFpEF (a smaller subset of ≈3800 individuals) for the genes linked to the deficit metabolome in each tissue (LV: ρ=0.24, P =5.6×10 −14 ; visceral adipose tissue: ρ=0.24, P =6.4×10 −16 ; skeletal muscle: ρ=0.22, P =9.5× 10 −12 ; kidney: ρ=0.20, P =9.5× 10 −5 ; liver: ρ=0.27, P = 4.2×10 −14 ), including some genes that we identified in Table 3 (eg, SLC22A3 , 70 MRPS16 85 ) in HFpEF.

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