ArticleProceedings of the National Academy of Sciences of the United States of America2022
Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Adherence to COVID-19 preventive measures in Sub-Saharan Africa during the 1st year of the pandemic: Pooled analysis of the International Citizen Project on COVID-19 (ICPCovid) surveys.Frontiers in public health · 2022Pooled it
- Local ancestry inference with poorly-matched reference panels.PLoS genetics · 2026Article
- Article
- Healthcare Development, Relaxed Natural Selection, and COVID-19 Infection Rates: An Evolutionary Population-Level Analysis.Health science reports · 2026Article
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- Forecasting framework for dominant SARS-CoV-2 strains before clade replacement using phylogeny-informed genetic distances.Frontiers in microbiology · 2025Article
- No evidence that ACE2 or TMPRSS2 drive population disparity in COVID risks.BMC medicine · 2024Article
- Enhancing portability of trans-ancestral polygenic risk scores through tissue-specific functional genomic data integration.PLoS genetics · 2024Article
- Comparative analysis of COVID-19 responses in Japan and Africa: diet, phytochemicals, vitamin D, and gut microbiota in reducing mortality-A systematic review and meta-analysis.Frontiers in nutrition · 2024Article
- Increased expression of SCARF genes favoring SARS-CoV-2 infection in key target organs in CKD.Clinical kidney journal · 2023Article
- Dataset of single nucleotide polymorphisms of immune-associated genes in patients with SARS-CoV-2 infection.PloS one · 2023Article
- The Penn Medicine BioBank: Towards a Genomics-Enabled Learning Healthcare System to Accelerate Precision Medicine in a Diverse Population.Journal of personalized medicine · 2022Article
- The Spike Protein of SARS-coV2 19B (S) Clade Mirrors Critical Features of Viral Adaptation and Coevolution.Microorganisms · 2022Article
- Pharmacogenomics at the post-pandemic: If not now, then when?Frontiers in pharmacology · 2022Article
- OM-85 Broncho-VaxomBiomedicines · 2021Article
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29 authors at 10 institutions in 6 countries.
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Abstract
Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (angiotensin converting enzyme 2 [ACE2], transmembrane protease serine 2 [TMPRSS2], dipeptidyl peptidase 4 [DPP4], and lymphocyte antigen 6 complex locus E [LY6E]). We analyzed data from 2,012 ethnically diverse Africans and 15,977 individuals of European and African ancestry with electronic health records and integrated with global data from the 1000 Genomes Project. At ACE2, we identified 41 nonsynonymous variants that were rare in most populations, several of which impact protein function. However, three nonsynonymous variants (rs138390800, rs147311723, and rs145437639) were common among central African hunter-gatherers from Cameroon (minor allele frequency 0.083 to 0.164) and are on haplotypes that exhibit signatures of positive selection. We identify signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage compared with the chimpanzee genome. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19. Our study provides insights into global variation at host genes related to SARS-CoV-2 infection, which have been shaped by natural selection in some populations, possibly due to prior viral infections.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.