| Title: |
Analysis of clinically relevant variants from ancestrally diverse Asian genomes |
| Authors: |
Chan, SH; Bylstra, Y; Teo, JX; Kuan, JL; Bertin, N; Gonzalez-Porta, M; Hebrard, M; Tirado-Magallanes, R; Tan, JHJ; Jeyakani, J; Li, Z; Chai, JF; Chong, YS; Davila, S; Goh, LL; Lee, ES; Wong, E; Wong, TY; Aung, T; Ban, KHK; Bellis, C; Chee, ML; Chew, WJ; Chin, CWL; Cook, SA; Dalan, R; Dorajoo, R; Drum, CL; Elliott, P; Eriksson, JG; Foo, R; Gardner, D; Gluckman, PD; Goh, DLM; Jain, K; Kam, S; Kassam, I; Lakshmanan, LN; Lee, CG; Lee, J; Lee, SC; Lee, YS; Li, H; Lim, CW; Lim, TH; Loh, M; Maurer-Stroh, S; Mina, TH; Mok, SQ; Ng, HK; Pua, CJ; Riboli, E; Rim, TH; Sabanayagam, C; Sim, WC; Subramaniam, T; Tan, ES; Tan, EK; Tantoso, E; Tay, D; Teo, YY; Tham, YC; Toh, LXG; Tsai, PK; van Dam, RM; Veeravalli, L; Khin-lin, GW; Wilm, A; Yang, C; Yap, F; Yew, YW; Prabhakar, S; Liu, J; Cheng, CY; Eisenhaber, B; Karnani, N; Leong, KP; Sim, X; Yeo, KK; Chambers, JC; Tai, ES; Tan, P; Jamuar, SS; Ngeow, J; Lim, WK |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2022 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://hdl.handle.net/11343/334994 |
| Availability: |
https://hdl.handle.net/11343/334994 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.B4807DB4 |
| Database: |
BASE |