Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality

Ying-Ju Lin^#^{1

2}, Ju-Pi Li^#^{3

4}, Yi-Ching Lai⁵, Ting-Yuan Liu⁶, Jian-Shiun Chiou^{7

8}, Hsing-Fang Lu^{6

9}, Kuyuri Ariyoshi^{9

10

11}, Chikashi Terao^{9

10

12}, Jai-Sing Yang¹³, Chen-Hsing Chou^{7

8}, Wen-Miin Liang⁸, I-Ching Chou^{2

14}, Chih-Te Ho¹⁵, Ting-Hsu Lin¹, Chiu-Chu Liao¹, Shao-Mei Huang¹, Fuu-Jen Tsai^{1

2

16

17}

Affiliations

¹ Department of Medical Research, Genetic Center, China Medical University Hospital, Taichung, Taiwan. (Y.-J.L., T.-H.L., C.-C.L., S.-M.H., F.-J.T.).
² School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. (Y.-J.L., I.-C.C., F.-J.T.).
³ Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan. (J.-P.L.).
⁴ Department of Pediatrics, Chung Shan Medical University, Taichung, Taiwan. (J.-P.L.).
⁵ Division of Cardiology, China Medical University Hospital, Taichung, Taiwan. (Y.-C.L.).
⁶ Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. (T.-Y.L., H.-F.L.).
⁷ PhD Program for Health Science and Industry, College of Health Care, China Medical University, Taichung, Taiwan. (J.-S.C., C.-H.C.).
⁸ Department of Health Services Administration, China Medical University, Taichung, Taiwan. (J.-S.C., C.-H.C., W.-M.L.).
⁹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (H.-F.L., K.A., C.T.).
¹⁰ Clinical Research Center, Shizuoka General Hospital, Japan (K.A., C.T.).
¹¹ Division of Medical Biophysics, Department of Biophysics, Graduate School of Health Sciences, Kobe University, Japan (K.A.).
¹² The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Japan (C.T.).
¹³ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. (J.-S.Y.).
¹⁴ Department of Pediatrics, China Medical University Children's Hospital, Taichung, Taiwan. (I.-C.C.).
¹⁵ Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan. (C.-T.H.).
¹⁶ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan. (F.-J.T.).
¹⁷ Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan (F.-J.T.).

^# Contributed equally.

PMID: 41058576
DOI: 10.1161/HYPERTENSIONAHA.125.25321

Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality

Ying-Ju Lin et al. Hypertension. 2025.

. 2025 Oct 8.

doi: 10.1161/HYPERTENSIONAHA.125.25321. Online ahead of print.

Authors

Affiliations

¹ Department of Medical Research, Genetic Center, China Medical University Hospital, Taichung, Taiwan. (Y.-J.L., T.-H.L., C.-C.L., S.-M.H., F.-J.T.).
² School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. (Y.-J.L., I.-C.C., F.-J.T.).
³ Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan. (J.-P.L.).
⁴ Department of Pediatrics, Chung Shan Medical University, Taichung, Taiwan. (J.-P.L.).
⁵ Division of Cardiology, China Medical University Hospital, Taichung, Taiwan. (Y.-C.L.).
⁶ Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. (T.-Y.L., H.-F.L.).
⁷ PhD Program for Health Science and Industry, College of Health Care, China Medical University, Taichung, Taiwan. (J.-S.C., C.-H.C.).
⁸ Department of Health Services Administration, China Medical University, Taichung, Taiwan. (J.-S.C., C.-H.C., W.-M.L.).
⁹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (H.-F.L., K.A., C.T.).
¹⁰ Clinical Research Center, Shizuoka General Hospital, Japan (K.A., C.T.).
¹¹ Division of Medical Biophysics, Department of Biophysics, Graduate School of Health Sciences, Kobe University, Japan (K.A.).
¹² The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Japan (C.T.).
¹³ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. (J.-S.Y.).
¹⁴ Department of Pediatrics, China Medical University Children's Hospital, Taichung, Taiwan. (I.-C.C.).
¹⁵ Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan. (C.-T.H.).
¹⁶ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan. (F.-J.T.).
¹⁷ Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan (F.-J.T.).

^# Contributed equally.

PMID: 41058576
DOI: 10.1161/HYPERTENSIONAHA.125.25321

Abstract

Background: Hypertension is a major health burden in East Asia. However, the genetic architecture and clinical implications of blood pressure (BP) traits remain underexplored beyond European-focused studies. This large-scale study aimed to investigate hypertension, systolic BP, and diastolic BP, to uncover genetic links to comorbidities and mortality in Han Taiwanese individuals.

Methods: This large-scale study used China Medical University Hospital biobank data and conducted genome-wide association studies on 25 523 hypertension cases and 47 522 controls, plus 66 236 individuals for systolic BP and 66 152 for diastolic BP. Cross-trait genetic correlations were assessed across 5 East Asian biobanks. Mendelian randomization and polygenic risk scores were applied to assess causality and predict clinical outcomes.

Results: We identified 8 loci and 36 genes for hypertension, 7 loci and 17 genes for systolic BP, and 9 loci and 26 genes for diastolic BP. ATP2B1 and FGF5 were common to all BP traits, implicating calcium signaling and vascular remodeling pathways. Cross-trait analyses showed shared genetic liability between BP traits and cardiovascular and metabolic comorbidities. Phenome-wide association studies confirmed strong associations with circulatory diseases. Mendelian randomization analyses demonstrated that elevated BP causally increases the risk of unstable angina pectoris. Polygenic risk scores predicted significantly higher risks and earlier onset of unstable angina pectoris, all-cause mortality, and cardiovascular mortality among individuals in the top polygenic risk score quintiles.

Conclusions: Our findings highlight the genetic basis of BP and comorbidities in East Asians, suggesting that BP genetic risk may inform future approaches to early risk assessment and prevention.

Keywords: blood pressure; cardiovascular diseases; genome-wide association study; hypertension; mortality.

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Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality

Affiliations

Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality

Authors

Affiliations

Abstract

LinkOut - more resources

Full Text Sources