Abstract

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk scores are constructed and validated for absolute risks prediction of T2D in Taiwanese population. In conclusion, our data-driven approach without a priori hypothesis is useful for novel gene discovery and validation on top of disease risk prediction for unique non-European population.

A phenome-wide association study and polygenic risk score analysis identifies several loci linked to metabolic disease and type 2 diabetes in the Taiwanese population.

Details

Title
Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes
Author
Lee, Chia-Jung 1 ; Chen, Ting-Huei 2 ; Lim, Aylwin Ming Wee 3   VIAFID ORCID Logo  ; Chang, Chien-Ching 4 ; Sie, Jia-Jyun 5 ; Chen, Pei-Lung 6 ; Chang, Su-Wei 7 ; Wu, Shang-Jung 4 ; Hsu, Chia-Lin 4 ; Hsieh, Ai-Ru 8 ; Yang, Wei-Shiung 9 ; Fann, Cathy S. J. 4 

1  Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (GRID:grid.482251.8) (ISNI:0000 0004 0633 7958); Washington University School of Medicine, Department of Pathology and Immunology, Saint Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
2  Laval University, Department of Mathematics and Statistics, Quebec, Canada (GRID:grid.23856.3a) (ISNI:0000 0004 1936 8390); Brain Research Centre (CERVO), Quebec, Canada (GRID:grid.23856.3a) 
3  Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (GRID:grid.482251.8) (ISNI:0000 0004 0633 7958); National Yang Ming Chiao Tung University and Academia Sinica, Taiwan International Graduate Program in Molecular Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017) 
4  Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (GRID:grid.482251.8) (ISNI:0000 0004 0633 7958) 
5  National Changhua University of Education, Department of Mathematics, Changhua, Taiwan (GRID:grid.412038.c) (ISNI:0000 0000 9193 1222) 
6  National Taiwan University, Graduate Institute of Medical Genomics and Proteomics, College of Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University Hospital, Department of Medical Genetics, Taipei, Taiwan (GRID:grid.412094.a) (ISNI:0000 0004 0572 7815); National Taiwan University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241) 
7  Chang Gung University, Clinical Informatics and Medical Statistics Research Center, Taoyuan, Taiwan (GRID:grid.145695.a) (ISNI:0000 0004 1798 0922); Chang Gung Memorial Hospital at Linkou, Department of Laboratory Medicine, Taoyuan, Taiwan (GRID:grid.454210.6) (ISNI:0000 0004 1756 1461) 
8  Tamkang University, Department of Statistics, New Taipei City, Taiwan (GRID:grid.264580.d) (ISNI:0000 0004 1937 1055) 
9  National Taiwan University, Graduate Institute of Medical Genomics and Proteomics, College of Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University Hospital, Department of Internal Medicine, Taipei, Taiwan (GRID:grid.412094.a) (ISNI:0000 0004 0572 7815) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-022-04168-0
ProQuest document ID
2731635908
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.