Analysis across Taiwan Biobank, Biobank Japan, and UK Biobank identifies hundreds of novel loci for 36 quantitative traits

Chia-Yen Chen; Tzu-Ting Chen; Yen-Chen Anne Feng; Mingrui Yu; Shu-Chin Lin; Ryan J Longchamps; Shi-Heng Wang; Yi-Hsiang Hsu; Hwai-I Yang; Po-Hsiu Kuo; Mark J Daly; Wei J Chen; Hailiang Huang; Tian Ge; Yen-Feng Lin

doi:10.1016/j.xgen.2023.100436

Analysis across Taiwan Biobank, Biobank Japan, and UK Biobank identifies hundreds of novel loci for 36 quantitative traits

Cell Genom. 2023 Nov 16;3(12):100436. doi: 10.1016/j.xgen.2023.100436. eCollection 2023 Dec 13.

Authors

Chia-Yen Chen¹, Tzu-Ting Chen², Yen-Chen Anne Feng³, Mingrui Yu⁴, Shu-Chin Lin², Ryan J Longchamps⁴, Shi-Heng Wang⁵, Yi-Hsiang Hsu⁶, Hwai-I Yang⁷, Po-Hsiu Kuo⁸, Mark J Daly⁹, Wei J Chen¹⁰, Hailiang Huang¹¹, Tian Ge¹², Yen-Feng Lin¹³

Affiliations

¹ Biogen, Cambridge, MA 02142, USA; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: [email protected].
² Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan.
³ Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100025, Taiwan; Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei 100025, Taiwan. Electronic address: [email protected].
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁵ National Center for Geriatrics and Welfare Research, National Health Research Institutes, Miaoli 35053, Taiwan; Department of Public Health, College of Public Health, China Medical University, Taichung 40678, Taiwan.
⁶ Marcus Institute for Aging Research and Harvard Medical School, Boston, MA 02131, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Harvard School of Public Health, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁷ Genomics Research Center, Academia Sinica, Taipei 115201, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei 112304, Taiwan; Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan; Biomedical Translation Research Center, Academia Sinica, Taipei 115021, Taiwan.
⁸ Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100025, Taiwan; Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei 106319, Taiwan.
⁹ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00014 Helsinki, Finland.
¹⁰ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan; Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100025, Taiwan; Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei 106319, Taiwan.
¹¹ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. Electronic address: [email protected].
¹² Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: [email protected].
¹³ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan; Department of Public Health & Medical Humanities, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. Electronic address: [email protected].

Abstract

Genome-wide association studies (GWASs) have identified tens of thousands of genetic loci associated with human complex traits. However, the majority of GWASs were conducted in individuals of European ancestries. Failure to capture global genetic diversity has limited genomic discovery and has impeded equitable delivery of genomic knowledge to diverse populations. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia. We identified 968 novel genetic loci, pinpointed novel causal variants through statistical fine-mapping, compared the genetic architecture across TWB, Biobank Japan, and UK Biobank, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores in disease risk prediction. These results demonstrated the potential to advance discovery through diversifying GWAS populations and provided insights into the common genetic basis of human complex traits in East Asia.

Keywords: Taiwan Biobank; cross-ancestry GWAS; multi-polygenic score prediction; quantitative traits.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding