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Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure: a mediated Mendelian randomization study†

Lei Pang

Lei Pang

  • Department of Urology, The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital)Taiyuan, China
  • First Clinical Medical College of Shanxi Medical UniversityTaiyuan, China
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Pang, Lei
, 
Zi-Jun Ding

Zi-Jun Ding

Department of Neonatology, Shanxi Children’s HospitalTaiyuan, China
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Ding, Zi-Jun
, 
Hong-Qiang Chai

Hong-Qiang Chai

Department of Urology, The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital)Taiyuan, China
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Chai, Hong-Qiang
, 
Fei Li

Fei Li

Department of Urology, The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital)Taiyuan, China
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Li, Fei
, 
Ming Wu

Ming Wu

Department of Urology, The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital)Taiyuan, China
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Wu, Ming
 and 
Wei-Bing Shuang

Wei-Bing Shuang

  • First Clinical Medical College of Shanxi Medical UniversityTaiyuan, China
  • Department of Urology, The First Hospital of Shanxi Medical UniversityTaiyuan, China
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Shuang, Wei-Bing
  
Sep 16, 2024
Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure: a mediated Mendelian randomization study†'s Cover Image
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Article Category: Original article
Published Online: Sep 16, 2024
Page range: 285 - 294
Received: Feb 03, 2024
Accepted: Apr 18, 2024
DOI: https://doi.org/10.2478/fon-2024-0031
Keywords
© 2024 Lei Pang et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1.

Study design. Note: IVW, inverse variance weighted; MR, Mendelian randomization.
Study design. Note: IVW, inverse variance weighted; MR, Mendelian randomization.

Figure 2.

Schematic diagram of causality.
Schematic diagram of causality.

Figure 3.

(a) MR-estimated effects of DBP on each mediator separately, presented as β/OR with 95% CI. (b) MR-estimated effects of each mediator separately on HRDRF after MVMR adjustment for DBP, presented as β/OR with 95% CI. (c) MR estimated effects of indirect effects of each mediator separately, by product of coefficients method with delta method-estimated 95% CIs. MR estimated proportions mediated (%) are presented with 95% CIs. Note: AHD, atherosclerotic heart disease; DBP, diastolic blood pressure; HA, heart arrhythmia; HF, heart failure; HRDRF, hypertensive renal disease with renal failure; MR, Mendelian randomization.
(a) MR-estimated effects of DBP on each mediator separately, presented as β/OR with 95% CI. (b) MR-estimated effects of each mediator separately on HRDRF after MVMR adjustment for DBP, presented as β/OR with 95% CI. (c) MR estimated effects of indirect effects of each mediator separately, by product of coefficients method with delta method-estimated 95% CIs. MR estimated proportions mediated (%) are presented with 95% CIs. Note: AHD, atherosclerotic heart disease; DBP, diastolic blood pressure; HA, heart arrhythmia; HF, heart failure; HRDRF, hypertensive renal disease with renal failure; MR, Mendelian randomization.

Figure 4.

(A) MR effect size for DBP on HRDRF. (B) SNP effect on DBP. (C) MR funnel plot of DBP on HRDRF. (D) MR leave-one-out sensitivity analysis of DBP on HRDRF. Note: DBP, diastolic blood pressure; HRDRF, hypertensive renal disease with renal failure; MR, Mendelian randomization.
(A) MR effect size for DBP on HRDRF. (B) SNP effect on DBP. (C) MR funnel plot of DBP on HRDRF. (D) MR leave-one-out sensitivity analysis of DBP on HRDRF. Note: DBP, diastolic blood pressure; HRDRF, hypertensive renal disease with renal failure; MR, Mendelian randomization.

Brief description for the GWAS data used in this study_

GWAS ID Year Trait Consortium Sample size Number of SNPs
ieu-b-39 2018 DBP International Consortium of Blood Pressure 757,601 7,160,619
ebi-a-GCST009541 2020 HF NA 977,323 7,773,021
ukb-b-3703 2018 HA MRC-IEU 462,933 9,851,867
ukb-b-1668 2018 AHD MRC-IEU 463,010 9,851,867
ukb-b-19955 2018 HRDRF MRC-IEU 463,010 9,851,867

Information on instrumental variables of HF (394 SNPs)_

SNP EA OA beta eaf chr pos se p
rs10048404 T C −0.1096 0.3694 18 54578482 0.0183 2.00e–09
rs10054208 T C 0.1187 0.3617 5 55688992 0.0185 1.49e–10
rs10062049 T C 0.2208 0.1359 5 61553881 0.0255 4.50e–18
rs1006545 T G 0.3633 0.8875 10 1.03e+08 0.0275 7.96e–40
rs10069690 T C 0.1615 0.2581 5 1279790 0.021 1.42e–14
rs10087280 G A −0.1381 0.1683 8 49391836 0.0232 2.54e–09
rs10164193 G T 0.2196 0.0777 18 31161426 0.0327 1.87e–11
rs10279432 A C 0.1178 0.6234 7 7279010 0.018 5.73e–11
rs1035673 C T −0.1625 0.6032 2 2.19e+08 0.0176 3.00e–20
rs1039897 A G −0.1085 0.6503 2 2.2e+08 0.0183 3.26e–09
rs9508495 T C −0.1944 0.7569 13 30146201 0.0204 1.34e–21
rs9526707 A G −0.1217 0.3222 13 51489186 0.0186 6.59e–11
rs962369 C T −0.1684 0.3013 11 27734420 0.0189 6.02e–19
rs964941 A G 0.1726 0.5183 1 2.28e+08 0.0174 3.31e–23
rs9791312 C A 0.1225 0.3452 6 1.43e+08 0.0184 2.89e–11
rs9841978 A G 0.1766 0.3251 3 53730735 0.0185 1.12e–21
rs9900637 A C 0.0992 0.4961 17 3951975 0.0176 1.73e–08
rs9918907 G A 0.1188 0.2162 8 1.25e+08 0.021 1.59e–08
rs9932220 A G −0.1591 0.2177 16 51758116 0.021 3.76e–14
rs9937801 C T −0.1554 0.4308 16 21088130 0.0174 4.81e–19

Information on instrumental variables of DBP (201 SNPs)_

SNP EA OA beta eaf chr pos se p
rs10048404 T C −0.1096 0.3694 18 54578482 0.0183 2.00e–09
rs10054208 T C 0.1187 0.3617 5 55688992 0.0185 1.49e–10
rs10279432 A C 0.1178 0.6234 7 7279010 0.018 5.73e–11
rs1035673 C T −0.1625 0.6032 2 2.19e+08 0.0176 3.00e–20
rs1039897 A G −0.1085 0.6503 2 2.2e+08 0.0183 3.26e–09
rs1049212 G A 0.1788 0.5694 16 4932929 0.0175 1.30e–24
rs10759697 A G 0.1308 0.4906 9 1.17e+08 0.0173 3.93e–14
rs10804330 C T −0.1331 0.4329 2 2.27e+08 0.0176 4.60e–14
rs10838702 T G 0.2375 0.3875 11 47410888 0.0178 1.27e–40
rs10873612 T C −0.1096 0.5961 15 26105602 0.0179 9.51e–10
rs9368 A C 0.1121 0.3871 12 56988342 0.0178 3.24e–10
rs9406076 T C 0.101 0.3278 6 8023804 0.0185 4.65e–08
rs9419374 G A −0.1164 0.646 10 1.34e+08 0.0185 3.44e–10
rs9526707 A G −0.1217 0.3222 13 51489186 0.0186 6.59e–11
rs964941 A G 0.1726 0.5183 1 2.28e+08 0.0174 3.31e–23
rs9791312 C A 0.1225 0.3452 6 1.43e+08 0.0184 2.89e–11
rs9841978 A G 0.1766 0.3251 3 53730735 0.0185 1.12e–21
rs9889262 A T 0.2283 0.3666 17 47398070 0.018 7.11e–37
rs9900637 A C 0.0992 0.4961 17 3951975 0.0176 1.73e–08
rs990619 G C 0.1592 0.5234 4 1.57e+08 0.0173 2.90e–20
rs9937801 C T −0.1554 0.4308 16 21088130 0.0174 4.81e–19

Mediation analysis results_

Exposure Outcome OR 95% CI P-value
HF HRDRF 1.0017 1.0004–1.0030 0.0108

Results of DBP on HRDRF and related indicators_

Exposure Outcome IVW WME
OR 95% CI P-value OR 95% CI P-value
DBP HRDRF 1.0002 1.0001–1.0003 1.8076e–05 1.0002 1.0001–1.0004 1.1617e–03
DBP HF 1.0295 1.0221–1.0370 2.5292e–15 1.0394 1.0300–1.0488 4.9222e–17
DBP HA 1.0001 1.0000–1.00022 0.0932 1.0000 0.9999–1.00024 0.7875
DBP AHD 1.0017 1.0014–1.0020 1.4957e–29 1.0017 1.0013–1.0020 1.1820e–20
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