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Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Author

Listed:
  • Sock Hoai Chan

    (National Cancer Centre Singapore
    Duke-NUS Medical School
    Nanyang Technological University)

  • Yasmin Bylstra

    (SingHealth Duke-NUS Institute of Precision Medicine)

  • Jing Xian Teo

    (SingHealth Duke-NUS Institute of Precision Medicine)

  • Jyn Ling Kuan

    (SingHealth Duke-NUS Institute of Precision Medicine)

  • Nicolas Bertin

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Mar Gonzalez-Porta

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Maxime Hebrard

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Roberto Tirado-Magallanes

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Joanna Hui Juan Tan

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Justin Jeyakani

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Zhihui Li

    (Genome Research Informatics & Data Science Platform, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Jin Fang Chai

    (National University of Singapore)

  • Yap Seng Chong

    (National University of Singapore
    Singapore Institute for Clinical Sciences)

  • Sonia Davila

    (SingHealth Duke-NUS Institute of Precision Medicine
    Duke-NUS Medical School
    SingHealth Duke-NUS Genomic Medicine Centre)

  • Liuh Ling Goh

    (Personalized Medicine Service, Tan Tock Seng Hospital)

  • Eng Sing Lee

    (Nanyang Technological University
    National Healthcare Group Polyclinics)

  • Eleanor Wong

    (Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Tien Yin Wong

    (Singapore Eye Research Institute, Singapore National Eye Centre)

  • Shyam Prabhakar

    (Laboratory of Systems Biology and Data Analytics, Genome Institute of Singapore, Agency for Science, Technology and Research)

  • Jianjun Liu

    (Human Genomics, Genome Institute of Singapore, Agency for Science, Technology and Research
    National University of Singapore)

  • Ching-Yu Cheng

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School)

  • Birgit Eisenhaber

    (Genome Institute of Singapore, Agency for Science, Technology and Research
    Bioinformatics Institute, Agency for Science, Technology and Research)

  • Neerja Karnani

    (Human Development, Singapore Institute for Clinical Sciences
    Clinical Data Engagement, Bioinformatics Institute, Agency for Science, Technology and Research
    National University of Singapore)

  • Khai Pang Leong

    (Personalized Medicine Service, Tan Tock Seng Hospital
    Tan Tock Seng Hospital)

  • Xueling Sim

    (National University of Singapore)

  • Khung Keong Yeo

    (SingHealth Duke-NUS Institute of Precision Medicine
    National Heart Centre Singapore
    Duke-NUS Medical School)

  • John C. Chambers

    (Nanyang Technological University
    Precision Health Research Singapore (PRECISE)
    Imperial College London)

  • E-Shyong Tai

    (National University of Singapore
    National University of Singapore
    Duke-NUS Medical School
    Precision Health Research Singapore (PRECISE))

  • Patrick Tan

    (SingHealth Duke-NUS Institute of Precision Medicine
    Genome Institute of Singapore, Agency for Science, Technology and Research
    Precision Health Research Singapore (PRECISE)
    Duke-NUS Medical School)

  • Saumya S. Jamuar

    (SingHealth Duke-NUS Institute of Precision Medicine
    SingHealth Duke-NUS Genomic Medicine Centre
    KK Women’s and Children’s Hospital
    Duke-NUS Medical School)

  • Joanne Ngeow

    (National Cancer Centre Singapore
    Duke-NUS Medical School
    Nanyang Technological University
    Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research)

  • Weng Khong Lim

    (SingHealth Duke-NUS Institute of Precision Medicine
    SingHealth Duke-NUS Genomic Medicine Centre
    Duke-NUS Medical School)

Abstract

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.

Suggested Citation

  • Sock Hoai Chan & Yasmin Bylstra & Jing Xian Teo & Jyn Ling Kuan & Nicolas Bertin & Mar Gonzalez-Porta & Maxime Hebrard & Roberto Tirado-Magallanes & Joanna Hui Juan Tan & Justin Jeyakani & Zhihui Li &, 2022. "Analysis of clinically relevant variants from ancestrally diverse Asian genomes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34116-9
    DOI: 10.1038/s41467-022-34116-9
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    as
    1. Monkol Lek & Konrad J. Karczewski & Eric V. Minikel & Kaitlin E. Samocha & Eric Banks & Timothy Fennell & Anne H. O’Donnell-Luria & James S. Ware & Andrew J. Hill & Beryl B. Cummings & Taru Tukiainen , 2016. "Analysis of protein-coding genetic variation in 60,706 humans," Nature, Nature, vol. 536(7616), pages 285-291, August.
    2. Alice B. Popejoy, 2021. "Too many scientists still say Caucasian," Nature, Nature, vol. 596(7873), pages 463-463, August.
    3. Quanli Wang & Ryan S. Dhindsa & Keren Carss & Andrew R. Harper & Abhishek Nag & Ioanna Tachmazidou & Dimitrios Vitsios & Sri V. V. Deevi & Alex Mackay & Daniel Muthas & Michael Hühn & Susan Monkley & , 2021. "Rare variant contribution to human disease in 281,104 UK Biobank exomes," Nature, Nature, vol. 597(7877), pages 527-532, September.
    4. Ibrahim Numanagić & Salem Malikić & Michael Ford & Xiang Qin & Lorraine Toji & Milan Radovich & Todd C. Skaar & Victoria M. Pratt & Bonnie Berger & Steve Scherer & S. Cenk Sahinalp, 2018. "Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    5. Hannes P. Eggertsson & Snaedis Kristmundsdottir & Doruk Beyter & Hakon Jonsson & Astros Skuladottir & Marteinn T. Hardarson & Daniel F. Gudbjartsson & Kari Stefansson & Bjarni V. Halldorsson & Pall Me, 2019. "GraphTyper2 enables population-scale genotyping of structural variation using pangenome graphs," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
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