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†

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

1 Note: AHD, atherosclerotic heart disease; DBP, diastolic blood pressure; HA, heart arrhythmia; HF, heart failure; HRDRF, hypertensive renal disease with renal failure.

Table 2.

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

1 Note: DBP, diastolic blood pressure.

Table 3.

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

1 Note: HF, heart failure.

Table 4.

Results of DBP on HRDRF and related indicators.

Exposure	Outcome	IVW			WME
Exposure	Outcome	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

1 Note: AHD, atherosclerotic heart disease; DBP, diastolic blood pressure; HA, heart arrhythmia; HF, heart failure; HRDRF, hypertensive renal disease with renal failure; IVW, inverse variance weighted.

(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.

Table 5.

Mediation analysis results.

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

1 Note: HF, heart failure; HRDRF, hypertensive renal disease with renal failure.

(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.

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DOI: https://doi.org/10.2478/fon-2024-0031 | Journal eISSN: 2544-8994 | Journal ISSN: 2097-5368

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Language: English

Page range: 285 - 294

Submitted on: Feb 3, 2024

Accepted on: Apr 18, 2024

Published on: Sep 16, 2024

Published by: Shanxi Medical Periodical Press

In partnership with: Paradigm Publishing Services

Keywords:

atherosclerotic heart disease,

diastolic blood pressure,

heart arrhythmia,

heart failure,

hypertensive renal disease with renal failure,

Mendelian randomization

Related subjects:

Medicine,

Assistive professions, nursing

© 2024 Lei Pang, Zi-Jun Ding, Hong-Qiang Chai, Fei Li, Ming Wu, Wei-Bing Shuang, published by Shanxi Medical Periodical Press
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 11 (2024): Issue 3 (September 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†

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Figure 1.

Table 1.

Table 2.

Table 3.

Table 4.

Figure 2.

Figure 3.

Table 5.

Figure 4.

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