Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes

Chia-Jung Lee; Ting-Huei Chen; Aylwin Ming Wee Lim; Chien-Ching Chang; Jia-Jyun Sie; Pei-Lung Chen; Su-Wei Chang; Shang-Jung Wu; Chia-Lin Hsu; Ai-Ru Hsieh; Wei-Shiung Yang; Cathy S J Fann

doi:10.1038/s42003-022-04168-0

Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes

Commun Biol. 2022 Nov 3;5(1):1175. doi: 10.1038/s42003-022-04168-0.

Authors

Chia-Jung Lee^#^{1

2}, Ting-Huei Chen^#^{3

4}, Aylwin Ming Wee Lim^{1

5}, Chien-Ching Chang¹, Jia-Jyun Sie⁶, Pei-Lung Chen^{7

8

9}, Su-Wei Chang^{10

11}, Shang-Jung Wu¹, Chia-Lin Hsu¹, Ai-Ru Hsieh¹², Wei-Shiung Yang^{13

14

15}, Cathy S J Fann¹⁶

Affiliations

¹ Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
² Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
³ Department of Mathematics and Statistics, Laval University, Quebec, QC, G1V0A6, Canada.
⁴ Brain Research Centre (CERVO), Quebec, QC, G1V0A6, Canada.
⁵ Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, 115, Taiwan.
⁶ Department of Mathematics, National Changhua University of Education, Changhua, Taiwan.
⁷ Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, 10617, Taiwan.
⁸ Department of Medical Genetics, National Taiwan University Hospital, Taipei, 100225, Taiwan.
⁹ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 10617, Taiwan.
¹⁰ Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, 333, Taiwan.
¹¹ Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan.
¹² Department of Statistics, Tamkang University, New Taipei City, 251301, Taiwan. airudropbox@gmail.com.
¹³ Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, 10617, Taiwan. wsyang@ntu.edu.tw.
¹⁴ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 10617, Taiwan. wsyang@ntu.edu.tw.
¹⁵ Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100225, Taiwan. wsyang@ntu.edu.tw.
¹⁶ Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan. csjfann@ibms.sinica.edu.tw.

^# Contributed equally.

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 HbA_1c) 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Specimen Banks
Blood Glucose / genetics
Carbon-Carbon Lyases / genetics
Diabetes Mellitus, Type 2* / genetics
Genome-Wide Association Study*
Humans
Polymorphism, Single Nucleotide
Risk Factors
Taiwan / epidemiology

Substances

Blood Glucose
HACL1 protein, human
Carbon-Carbon Lyases

Abstract

Publication types

MeSH terms

Substances

Grants and funding