The ethnogeographic variability of genetic factors underlying G6PD deficiency

Maria Koromina, Maria Theodora Pandi, Peter J. van der Spek, George P. Patrinos, Volker M. Lauschke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
54 Downloads (Pure)

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency caused by genetic variants in the G6PD gene, constitutes the most common enzymopathy worldwide, affecting approximately 5% of the global population. While carriers are mostly asymptomatic, they are at substantial risk of acute hemolytic anemia upon certain infections or exposure to various medications. As such, information about G6PD activity status in a given patient can constitute an important parameter to guide clinical decision-making. Here, we leveraged whole genome sequencing data from 142,069 unrelated individuals across seven human populations to provide a global comprehensive map of G6PD variability. By integrating established functional classifications with stringent computational predictions using 13 partly orthogonal algorithms for uncharacterized and novel variants, we reveal the large extent of ethnogeographic variability in G6PD deficiency and highlight its population-specific genetic composition. Overall, estimated disease prevalence in males ranged between 12.2% in Africans, 2.7–3.5% across Asia and 2.1% in Middle Easterners to < 0.3% in Europeans, Finnish and Amish. In Africans, the major deficient alleles were A-202A/376 G (minor allele frequency 11.6%) and A-968 C/376 G (0.5%). In contrast, G6PD deficiency in Middle Easterners was primarily due to the Mediterranean allele (1.3%) and the population-specific Cairo variant (0.4%). In South Asia, the most prevalent deficient alleles were Mediterranean (1.7%), Kerala (1.1%), Gond (0.9%) and Orissa (0.2%), whereas in East Asian populations the Canton (1.1%), Kaiping (0.7%) and Viangchan (0.3%) variants were predominant. Combined, our analyses provide a large dataset of G6PD variability across major ethnogeographic groups and can instruct population-specific genotyping strategies to optimize genetically guided therapeutic interventions.

Original languageEnglish
Article number105904
JournalPharmacological Research
Volume173
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Funding Information:
V.M.L. is funded by the Swedish Research Council [grant agreement numbers: 2016?01153, 2016?01154 and 2019?01837], by the EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant number 875510) and by the Robert Bosch Foundation, Stuttgart, Germany. G.P.P. is funded by the European Union's Horizon 2020 research and innovation program Ubiquitous Pharmacogenomics (grant agreement number 668353). The authors also wish to acknowledge Mrs Zoi Gkizarioti and Mr Konstantinos Petropoulos for providing useful literature material regarding the assessed G6PD haplotypes. Maria Koromina: Data curation, Formal analysis, Methodology, Software, Writing - original draft; Writing - review & editing, Maria Theodora Pandi: Methodology, Software, Peter J. van der Spek: Supervision, George P. Patrinos: Conceptualization, Funding acquisition, Supervision, Writing - review & editing, Volker M. Lauschke: Conceptualization, Funding acquisition, Supervision, Visualization, Writing - review & editing.

Funding Information:
V.M.L. is funded by the Swedish Research Council [grant agreement numbers: 2016–01153 , 2016–01154 and 2019–01837 ], by the EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant number 875510 ) and by the Robert Bosch Foundation, Stuttgart, Germany. G.P.P. is funded by the European Union’s Horizon 2020 research and innovation program Ubiquitous Pharmacogenomics (grant agreement number 668353 ). The authors also wish to acknowledge Mrs Zoi Gkizarioti and Mr Konstantinos Petropoulos for providing useful literature material regarding the assessed G6PD haplotypes.

Publisher Copyright:
© 2021 The Authors

Fingerprint

Dive into the research topics of 'The ethnogeographic variability of genetic factors underlying G6PD deficiency'. Together they form a unique fingerprint.

Cite this