Dataset Information

Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

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.

SUBMITTER: Chan SH

PROVIDER: S-EPMC9637116 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

Chan Sock Hoai SH Bylstra Yasmin Y Teo Jing Xian JX Kuan Jyn Ling JL Bertin Nicolas N Gonzalez-Porta Mar M Hebrard Maxime M Tirado-Magallanes Roberto R Tan Joanna Hui Juan JHJ Jeyakani Justin J Li Zhihui Z Chai Jin Fang JF Chong Yap Seng YS Davila Sonia S Goh Liuh Ling LL Lee Eng Sing ES Wong Eleanor E Wong Tien Yin TY Prabhakar Shyam S Liu Jianjun J Cheng Ching-Yu CY Eisenhaber Birgit B Karnani Neerja N Leong Khai Pang KP Sim Xueling X Yeo Khung Keong KK Chambers John C JC Tai E-Shyong ES Tan Patrick P Jamuar Saumya S SS Ngeow Joanne J Lim Weng Khong WK

Nature communications 20221105 1

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. ...[more]

PMID: 36335097

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Dataset Information

Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

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Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

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