Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals

doi:10.1002/oby.24335

. 2025 Aug 14.

doi: 10.1002/oby.24335. Online ahead of print.

Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals

Ying-Ju Lin^{1

2}, Ju-Pi Li^{3

4}, Ting-Yuan Liu⁵, Jian-Shiun Chiou^{6

7}, Hsing-Fang Lu^{5

8}, Kuyuri Ariyoshi^{8

9}, Shunsuke Uchiyama⁸, Chikashi Terao^{8

10

11}, Jai-Sing Yang¹², Chen-Hsing Chou^{6

7}, Wen-Miin Liang⁷, I-Ching Chou^{2

13

14}, Cheng-Wen Lin^{6

15}, Ting-Hsu Lin¹, Chiu-Chu Liao¹, Shao-Mei Huang¹, Fuu-Jen Tsai^{1

2

16

17}

Affiliations

¹ Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
² School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
³ Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁴ Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁵ Million-person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁶ PhD Program for Health Science and Industry, College of Health Care, China Medical University, Taichung, Taiwan.
⁷ Department of Health Services Administration, China Medical University, Taichung, Taiwan.
⁸ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁹ Division of Medical Biophysics, Department of Biophysics, Graduate School of Health Sciences, Kobe University, Kobe, Japan.
¹⁰ Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
¹¹ Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
¹² Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹³ Department of Pediatric Neurology, China Medical University Children's Hospital, Taichung, Taiwan.
¹⁴ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
¹⁵ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
¹⁶ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan.
¹⁷ Department of Medical Laboratory Science & Biotechnology, Asia University, Taichung, Taiwan.

PMID: 40808477
DOI: 10.1002/oby.24335

Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals

Ying-Ju Lin et al. Obesity (Silver Spring). 2025.

. 2025 Aug 14.

doi: 10.1002/oby.24335. Online ahead of print.

Authors

Affiliations

¹ Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
² School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
³ Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁴ Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁵ Million-person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁶ PhD Program for Health Science and Industry, College of Health Care, China Medical University, Taichung, Taiwan.
⁷ Department of Health Services Administration, China Medical University, Taichung, Taiwan.
⁸ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁹ Division of Medical Biophysics, Department of Biophysics, Graduate School of Health Sciences, Kobe University, Kobe, Japan.
¹⁰ Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
¹¹ Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
¹² Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹³ Department of Pediatric Neurology, China Medical University Children's Hospital, Taichung, Taiwan.
¹⁴ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
¹⁵ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
¹⁶ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan.
¹⁷ Department of Medical Laboratory Science & Biotechnology, Asia University, Taichung, Taiwan.

PMID: 40808477
DOI: 10.1002/oby.24335

Abstract

Objective: Although associations of adiposity with metabolic, cardiovascular, and liver diseases are known, the genetic links, causal effects, and polygenic risk score (PRS) predictions for these health conditions in East Asian individuals remain unclear.

Methods: We conducted genome-wide association studies of BMI (n = 95,488) and body fat percentage (BFP; n = 83,448) in Taiwanese individuals from Taiwan Biobank data, followed by cross-trait genetic correlation and bidirectional Mendelian randomization in four East Asian biobanks. BMI and BFP PRS were constructed and validated in the China Medical University Hospital and Biobank Japan databases.

Results: We identified 41 BMI and 22 BFP loci, including novel loci. Genetically predicted higher adiposity correlated with increased risk of metabolic syndrome, cardiovascular disease, hypertension, and elevated liver enzymes. Bidirectional Mendelian randomization revealed a causal effect of adiposity on glycosylated hemoglobin, systolic blood pressure, liver enzymes, and cholelithiasis, with no reverse causality. After adjusting for type 2 diabetes, the effect on glycemic traits diminished, suggesting a strong influence of diabetes-related loci. BMI and BFP PRS robustly predicted higher risk and earlier onset of type 2 diabetes, hypertension, cholelithiasis, and liver dysfunction in East Asian individuals.

Conclusions: These findings reveal novel adiposity loci and underscore the clinical utility of adiposity-related genetics for personalized health.

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References

REFERENCES

1. Zamosky L. The obesity epidemic. While America swallows $147 billion in obesity‐related healthcare costs, physicians called on to confront the crisis. Med Econ. 2013;90:14‐17.
1. Bluher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15:288‐298.
1. Lin WY, Chan CC, Liu YL, Yang AC, Tsai SJ, Kuo PH. Performing different kinds of physical exercise differentially attenuates the genetic effects on obesity measures: evidence from 18,424 Taiwan Biobank participants. PLoS Genet. 2019;15:e1008277.
1. Ansari S, Haboubi H, Haboubi N. Adult obesity complications: challenges and clinical impact. Ther Adv Endocrinol Metab. 2020;11:2042018820934955. doi:10.1177/2042018820934955
1. Huang J, Huffman JE, Huang Y, et al. Genomics and phenomics of body mass index reveals a complex disease network. Nat Commun. 2022;13:7973.

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[1] Zamosky L. The obesity epidemic. While America swallows $147 billion in obesity‐related healthcare costs, physicians called on to confront the crisis. Med Econ. 2013;90:14‐17.

[2] Zamosky L. The obesity epidemic. While America swallows $147 billion in obesity‐related healthcare costs, physicians called on to confront the crisis. Med Econ. 2013;90:14‐17.

[3] Bluher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15:288‐298.

[4] Bluher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15:288‐298.

[5] Lin WY, Chan CC, Liu YL, Yang AC, Tsai SJ, Kuo PH. Performing different kinds of physical exercise differentially attenuates the genetic effects on obesity measures: evidence from 18,424 Taiwan Biobank participants. PLoS Genet. 2019;15:e1008277.

[6] Lin WY, Chan CC, Liu YL, Yang AC, Tsai SJ, Kuo PH. Performing different kinds of physical exercise differentially attenuates the genetic effects on obesity measures: evidence from 18,424 Taiwan Biobank participants. PLoS Genet. 2019;15:e1008277.

[7] Ansari S, Haboubi H, Haboubi N. Adult obesity complications: challenges and clinical impact. Ther Adv Endocrinol Metab. 2020;11:2042018820934955. doi:10.1177/2042018820934955

[8] Ansari S, Haboubi H, Haboubi N. Adult obesity complications: challenges and clinical impact. Ther Adv Endocrinol Metab. 2020;11:2042018820934955. doi:10.1177/2042018820934955

[9] Huang J, Huffman JE, Huang Y, et al. Genomics and phenomics of body mass index reveals a complex disease network. Nat Commun. 2022;13:7973.

[10] Huang J, Huffman JE, Huang Y, et al. Genomics and phenomics of body mass index reveals a complex disease network. Nat Commun. 2022;13:7973.

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Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals

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Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals

Authors

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Abstract

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References

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