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Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures

Author

Listed:
  • Yon Ho Jee

    (Harvard T.H. Chan School of Public Health)

  • Ying Wang

    (Massachusetts General Hospital
    Broad Institute of MIT and Harvard)

  • Keum Ji Jung

    (Yonsei University)

  • Ji-Young Lee

    (Yonsei University)

  • Heejin Kimm

    (Yonsei University)

  • Rui Duan

    (Harvard T.H. Chan School of Public Health)

  • Alkes L. Price

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Broad Institute of MIT and Harvard)

  • Alicia R. Martin

    (Massachusetts General Hospital
    Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health
    National Institutes of Health)

Abstract

Genome-wide association studies (GWAS) have predominantly focused on European ancestry populations, limiting biological discoveries across diverse populations. Here we report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 301 previously unreported genetic loci in KCPS2, including an association between thyroid-stimulating hormone and CD36. Meta-analysis with the Korean Genome and Epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 4588 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotropic missense variant in ALDH2, which fine-mapping identified as a likely causal variant for multiple traits. Our findings provide insights into the genetic architecture of complex traits in East Asian populations and highlight how broadening the population diversity of GWAS samples can aid discovery.

Suggested Citation

  • Yon Ho Jee & Ying Wang & Keum Ji Jung & Ji-Young Lee & Heejin Kimm & Rui Duan & Alkes L. Price & Alicia R. Martin & Peter Kraft, 2025. "Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59950-5
    DOI: 10.1038/s41467-025-59950-5
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    as
    1. Simone Rubinacci & Olivier Delaneau & Jonathan Marchini, 2020. "Genotype imputation using the Positional Burrows Wheeler Transform," PLOS Genetics, Public Library of Science, vol. 16(11), pages 1-19, November.
    2. Olivier Delaneau & Jean-François Zagury & Matthew R. Robinson & Jonathan L. Marchini & Emmanouil T. Dermitzakis, 2019. "Accurate, scalable and integrative haplotype estimation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Jian Zeng & Angli Xue & Longda Jiang & Luke R. Lloyd-Jones & Yang Wu & Huanwei Wang & Zhili Zheng & Loic Yengo & Kathryn E. Kemper & Michael E. Goddard & Naomi R. Wray & Peter M. Visscher & Jian Yang, 2021. "Widespread signatures of natural selection across human complex traits and functional genomic categories," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    5. Chris Wallace, 2021. "A more accurate method for colocalisation analysis allowing for multiple causal variants," PLOS Genetics, Public Library of Science, vol. 17(9), pages 1-11, September.
    6. repec:plo:pone00:0184295 is not listed on IDEAS
    7. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    8. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    9. Nana Matoba & Masato Akiyama & Kazuyoshi Ishigaki & Masahiro Kanai & Atsushi Takahashi & Yukihide Momozawa & Shiro Ikegawa & Masashi Ikeda & Nakao Iwata & Makoto Hirata & Koichi Matsuda & Yoshinori Mu, 2020. "GWAS of 165,084 Japanese individuals identified nine loci associated with dietary habits," Nature Human Behaviour, Nature, vol. 4(3), pages 308-316, March.
    10. Gloria Pascual & Diana Domínguez & Marc Elosúa-Bayes & Felipe Beckedorff & Carmelo Laudanna & Claudia Bigas & Delphine Douillet & Carolina Greco & Aikaterini Symeonidi & Inmaculada Hernández & Sara Ru, 2021. "Dietary palmitic acid promotes a prometastatic memory via Schwann cells," Nature, Nature, vol. 599(7885), pages 485-490, November.
    11. Alexander T. Williams & Jing Chen & Kayesha Coley & Chiara Batini & Abril Izquierdo & Richard Packer & Erik Abner & Stavroula Kanoni & David J. Shepherd & Robert C. Free & Edward J. Hollox & Nigel J. , 2023. "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Lin Xu & Chao Qiang Jiang & Kar Keung Cheng & Shiu Lun Ryan Au Yeung & Wei Sen Zhang & Tai Hing Lam & Catherine Mary Schooling, 2015. "Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study," PLOS ONE, Public Library of Science, vol. 10(9), pages 1-10, September.
    13. Yon Ho Jee & Sun Ju Lee & Keum Ji Jung & Sun Ha Jee, 2016. "Alcohol Intake and Serum Glucose Levels from the Perspective of a Mendelian Randomization Design: The KCPS-II Biobank," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-9, September.
    14. Loïc Yengo & Sailaja Vedantam & Eirini Marouli & Julia Sidorenko & Eric Bartell & Saori Sakaue & Marielisa Graff & Anders U. Eliasen & Yunxuan Jiang & Sridharan Raghavan & Jenkai Miao & Joshua D. Aria, 2022. "A saturated map of common genetic variants associated with human height," Nature, Nature, vol. 610(7933), pages 704-712, October.
    15. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    16. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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