Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study

TRAITS	PHENOTYPIC CODE	SAMPLE SIZE (CASES/CONTROLS)	ANCESTRY	R²(%) (TOTAL)	F (TOTAL)
Exposures
RA	ebi-a-GCST002318	14,361/42,923	European	0.1106	6365
IBD	finn-b-K11_IBD_STRICT	3,753/210,300	European	0.0079	1690
MS	ieu-b-18	47,429/68,374	European	0.0600	6978
SLE	ebi-a-GCST003156	5,201/9,066	European	0.3523	5081
T1D	ebi-a-GCST010681	9,266/15,574	European	0.2969	7486
Outcomes
PAH	finn-b-I9_HYPTENSPUL	125/162,837	European

[i] F = R²(N-K-1)/[K(1-R²)], R² = 2 × (1-EAF) × EAF×(b/SD)², SD = SE × N^1/2, where EAF is the effect allele frequency, b is the estimated effect on adipokines, N is the sample size of the GWAS and SE is the standard error of the estimated effect.

Table 2

Mendelian randomization estimates of RA, IBD, MS, SLE and T1D on the risk for PAH.

EXPOSURES	METHODS	SNPs (n)	OR	95%CI	p-VALUE
RA	MR Egger	109	1.31	0.84–2.06	0.236
	Weighted median	109	1.02	0.71–1.49	0.897
	IVW	109	1.27	1.01–1.61	0.042
	Simple mode	109	0.92	0.37–2.31	0.864
	Weighted mode	109	1.09	0.70–1.70	0.702
IBD	MR Egger	56	1.17	0.64–2.14	0.607
	Weighted median	56	1.14	0.79–1.66	0.484
	IVW	56	1.29	1.01–1.64	0.043
	Simple mode	56	1.11	0.52–2.39	0.789
	Weighted mode	56	1.05	0.56–1.97	0.878
MS	MR Egger	138	1.18	0.88–1.58	0.278
	Weighted median	138	1.07	0.77–1.50	0.675
	IVW	138	0.99	0.83–1.18	0.876
	Simple mode	138	1.11	0.57–2.17	0.751
	Weighted mode	138	1.09	0.78–1.52	0.597
SLE	MR Egger	92	0.93	0.71–1.22	0.601
SLE	Weighted median	92	0.86	0.70–1.05	0.145
	IVW	92	1.04	0.91–1.19	0.564
	Simple mode	92	0.78	0.54–1.13	0.193
	Weighted mode	92	0.84	0.66–1.07	0.164
T1D	MR Egger	175	1.07	0.92–1.23	0.380
	Weighted median	175	0.98	0.83–1.15	0.786
	IVW	175	1.10	1.00–1.21	0.061
	Simple mode	175	1.11	0.76–1.60	0.594
	Weighted mode	175	0.99	0.85–1.15	0.929

Table 3

Pleiotropy and heterogeneity test of the RA, IBD, MS, SLE and T1D IVs from PAH GWAS.

OUTCOMES	EXPOSURE	PLEIOTROPY TEST			HETEROGENEITY TEST
		MR-EGGER			MR-EGGER			INVERSE-VARIANCE WEIGHTED
		INTERCEPT	SE	P	Q	Q_-df	Q_-pval	Q	Q_-df	Q_-pval
PAH
	RA	–0.0045	0.0289	0.876	118.1564	107	0.217	118.1835	108	0.237
	IBD	0.0171	0.0520	0.743	42.9250	54	0.861	43.0334	55	0.879
	MS	–0.0326	0.0222	0.144	145.0318	136	0.282	147.3330	137	0.258
	SLE	0.0346	0.0363	0.344	101.7267	90	0.187	102.7517	91	0.188
	T1D	0.0118	0.0220	0.592	154.7772	173	0.837	155.0649	174	0.846

Table 4

Mendelian randomization results for effect of genetic liability to PAH on RA, IBD, MS, SLE and T1D.

OUTCOMES	METHODS	SNPs (n)	OR	95%CI	p-VALUE
RA	MR Egger	9	1.01	0.97–1.06	0.627
	Weighted median	9	1.01	0.98–1.03	0.678
	IVW	9	1.01	0.99–1.03	0.310
	Simple mode	9	1.00	0.97–1.03	0.921
	Weighted mode	9	1.00	0.99–1.03	0.805
IBD	MR Egger	12	1.06	1.00–1.13	0.066
	Weighted median	12	0.99	0.96–1.02	0.665
	IVW	12	0.99	0.97–1.02	0.513
	Simple mode	12	1.00	0.95–1.05	0.996
	Weighted mode	12	1.00	0.96–1.05	0.989
MS	MR Egger	7	1.02	0.96–1.08	0.497
	Weighted median	7	0.99	0.97–1.02	0.669
	IVW	7	0.99	0.97–1.02	0.621
	Simple mode	7	0.98	0.94–1.03	0.549
	Weighted mode	7	0.98	0.94–1.03	0.537
SLE	MR Egger	9	0.96	0.89–1.04	0.347
	Weighted median	9	1.03	0.99–1.07	0.180
	IVW	9	1.01	0.97–1.05	0.542
	Simple mode	9	1.03	0.95–1.11	0.523
	Weighted mode	9	1.03	0.98–1.08	0.252
T1D	MR Egger	12	1.02	0.96–1.08	0.591
	Weighted median	12	1.00	0.97–1.03	0.951
	IVW	12	1.01	0.99–1.04	0.262
	Simple mode	12	1.00	0.95–1.06	0.994
	Weighted mode	12	1.00	0.95–1.05	0.892

Articles in this issue

DOI: https://doi.org/10.5334/gh.1445 | Journal eISSN: 2211-8179

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Language: English

Submitted on: Aug 11, 2024

Accepted on: Jun 17, 2025

Published on: Jul 4, 2025

Published by: Ubiquity Press

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

Keywords:

Pulmonary Arterial Hypertension,

Autoimmune Diseases,

Rheumatoid Arthritis,

Inflammatory Bowel Disease,

Mendelian Randomization

© 2025 Chao Ma, Cheng Gong, Bin Wang, Yangmeina Li, Yongxiang Qian, Xiaoying Zhang, Dongmei Di, Min Wang, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 20 (2025): Issue 1

Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study

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Table 2

Table 3

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