TY - JOUR
T1 - Variation in 100 relevant pharmacogenes among emiratis with insights from understudied populations
AU - Al-Mahayri, Zeina N.
AU - Patrinos, George P.
AU - Wattanapokayakit, Sukanya
AU - Iemwimangsa, Nareenart
AU - Fukunaga, Koya
AU - Mushiroda, Taisei
AU - Chantratita, Wasun
AU - Ali, Bassam R.
N1 - Funding Information:
We acknowledge the valuable support of participants from the SEAPharm consortium. This work was supported by United Arab Emirates University funding grants (31R091) and (31M341), and the Thailand Center of Excellence for Life Sciences (TCELS) and the International Research Network (IRN60W0003) and Thailand Research Fund (TRF). We also acknowledge the continuous support of the UAE Ministry of Education for the PGx research.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Genetic variations have an established impact on the pharmacological response. Investigating this variation resulted in a compilation of variants in “pharmacogenes”. The emergence of next-generation sequencing facilitated large-scale pharmacogenomic studies and exhibited the extensive variability of pharmacogenes. Some rare and population-specific variants proved to be actionable, suggesting the significance of population pharmacogenomic research. A profound gap exists in the knowledge of pharmacogenomic variants enriched in some populations, including the United Arab Emirates (UAE). The current study aims to explore the landscape of variations in relevant pharmacogenes among healthy Emiratis. Through the resequencing of 100 pharmacogenes for 100 healthy Emiratis, we identified 1243 variants, of which 63% are rare (minor allele frequency ≤ 0.01), and 30% were unique. Filtering the variants according to Pharmacogenomics Knowledge Base (PharmGKB) annotations identified 27 diplotypes and 26 variants with an evident clinical relevance. Comparison with global data illustrated a significant deviation of allele frequencies in the UAE population. Understudied populations display a distinct allelic architecture and various rare and unique variants. We underscored pharmacogenes with the highest variation frequencies and provided investigators with a list of candidate genes for future studies. Population pharmacogenomic studies are imperative during the pursuit of global pharmacogenomics implementation.
AB - Genetic variations have an established impact on the pharmacological response. Investigating this variation resulted in a compilation of variants in “pharmacogenes”. The emergence of next-generation sequencing facilitated large-scale pharmacogenomic studies and exhibited the extensive variability of pharmacogenes. Some rare and population-specific variants proved to be actionable, suggesting the significance of population pharmacogenomic research. A profound gap exists in the knowledge of pharmacogenomic variants enriched in some populations, including the United Arab Emirates (UAE). The current study aims to explore the landscape of variations in relevant pharmacogenes among healthy Emiratis. Through the resequencing of 100 pharmacogenes for 100 healthy Emiratis, we identified 1243 variants, of which 63% are rare (minor allele frequency ≤ 0.01), and 30% were unique. Filtering the variants according to Pharmacogenomics Knowledge Base (PharmGKB) annotations identified 27 diplotypes and 26 variants with an evident clinical relevance. Comparison with global data illustrated a significant deviation of allele frequencies in the UAE population. Understudied populations display a distinct allelic architecture and various rare and unique variants. We underscored pharmacogenes with the highest variation frequencies and provided investigators with a list of candidate genes for future studies. Population pharmacogenomic studies are imperative during the pursuit of global pharmacogenomics implementation.
UR - http://www.scopus.com/inward/record.url?scp=85097073617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097073617&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-78231-3
DO - 10.1038/s41598-020-78231-3
M3 - Article
C2 - 33277594
AN - SCOPUS:85097073617
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 21310
ER -