Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations]
Background There is limited knowledge regarding African genetic drivers of disease due to prohibitive costs of large-scale genomic research in Africa. Methods We piloted a scalable virtual genotyped cohort in South Africa that was affordable in this resource-limited context, cost-effective, scalable...
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Wellcome
2025-01-01
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| Online Access: | https://wellcomeopenresearch.org/articles/9-620/v2 |
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| author | Robert J Wilkinson Francisco Lakay Nicki Tiffin Joel A Dave Catherine Riou Peter Raubenheimer Anna K Coussens Tsaone Tamuhla Melissa J Blumenthal Maleeka Abrahams |
| author_facet | Robert J Wilkinson Francisco Lakay Nicki Tiffin Joel A Dave Catherine Riou Peter Raubenheimer Anna K Coussens Tsaone Tamuhla Melissa J Blumenthal Maleeka Abrahams |
| author_sort | Robert J Wilkinson |
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| description | Background There is limited knowledge regarding African genetic drivers of disease due to prohibitive costs of large-scale genomic research in Africa. Methods We piloted a scalable virtual genotyped cohort in South Africa that was affordable in this resource-limited context, cost-effective, scalable virtual genotyped cohort in South Africa, with participant recruitment using a tiered informed consent model and DNA collection by buccal swab. Genotype data was generated using the H3Africa Illumina micro-array, and phenotype data was derived from routine health data of participants. We demonstrated feasibility of nested case control genome wide association studies using these data for phenotypes type 2 diabetes mellitus (T2DM) and severe COVID-19. Results 2267346 variants were analysed in 459 participant samples, of which 229 (66.8%) are female. 78.6% of SNPs and 74% of samples passed quality control (QC). Principal component analysis showed extensive ancestry admixture in study participants. Of the 343 samples that passed QC, 93 participants had T2DM and 63 had severe COVID-19. For 1780 previously published COVID-19-associated variants, 3 SNPs in the pre-imputation data and 23 SNPS in the imputed data were significantly associated with severe COVID-19 cases compared to controls (p<0.05). For 2755 published T2DM associated variants, 69 SNPs in the pre-imputation data and 419 SNPs in the imputed data were significantly associated with T2DM cases when compared to controls (p<0.05). Conclusions The results shown here are illustrative of what will be possible as the cohort expands in the future. Here we demonstrate the feasibility of this approach, recognising that the findings presented here are preliminary and require further validation once we have a sufficient sample size to improve statistical significance of findings. We implemented a genotyped population cohort with virtual follow up data in a resource-constrained African environment, demonstrating feasibility for scale up and novel health discoveries through nested case-control studies. |
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| institution | Kabale University |
| issn | 2398-502X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wellcome |
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| series | Wellcome Open Research |
| spelling | doaj-art-ce16ff14e6f54aaf923e4fb242e2d9b92025-02-08T01:00:00ZengWellcomeWellcome Open Research2398-502X2025-01-01925981Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations]Robert J Wilkinson0https://orcid.org/0000-0002-2753-1800Francisco Lakay1Nicki Tiffin2https://orcid.org/0000-0001-5083-2735Joel A Dave3https://orcid.org/0000-0003-3084-7408Catherine Riou4https://orcid.org/0000-0001-9679-0745Peter Raubenheimer5https://orcid.org/0000-0002-5416-1286Anna K Coussens6https://orcid.org/0000-0002-7086-2621Tsaone Tamuhla7https://orcid.org/0000-0001-5966-9153Melissa J Blumenthal8https://orcid.org/0000-0002-1865-0795Maleeka Abrahams9Wellcome CIDRI-Africa, Faculty of Health Sciences, University of Cape Town, Rondebosch, Western Cape, South AfricaWellcome CIDRI-Africa, Faculty of Health Sciences, University of Cape Town, Rondebosch, Western Cape, South AfricaSouth African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South AfricaDivision of Endocrinology, Department of Medicine, University of Cape Town, Rondebosch, Cape Town, South AfricaWellcome CIDRI-Africa, Faculty of Health Sciences, University of Cape Town, Rondebosch, Western Cape, South AfricaDivision of Endocrinology, Department of Medicine, University of Cape Town, Rondebosch, Cape Town, South AfricaWellcome CIDRI-Africa, Faculty of Health Sciences, University of Cape Town, Rondebosch, Western Cape, South AfricaSouth African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South AfricaInternational Centre for Genetic Engineering and Biotechnology, Cape Town, South AfricaDivision of Endocrinology, Department of Medicine, University of Cape Town, Rondebosch, Cape Town, South AfricaBackground There is limited knowledge regarding African genetic drivers of disease due to prohibitive costs of large-scale genomic research in Africa. Methods We piloted a scalable virtual genotyped cohort in South Africa that was affordable in this resource-limited context, cost-effective, scalable virtual genotyped cohort in South Africa, with participant recruitment using a tiered informed consent model and DNA collection by buccal swab. Genotype data was generated using the H3Africa Illumina micro-array, and phenotype data was derived from routine health data of participants. We demonstrated feasibility of nested case control genome wide association studies using these data for phenotypes type 2 diabetes mellitus (T2DM) and severe COVID-19. Results 2267346 variants were analysed in 459 participant samples, of which 229 (66.8%) are female. 78.6% of SNPs and 74% of samples passed quality control (QC). Principal component analysis showed extensive ancestry admixture in study participants. Of the 343 samples that passed QC, 93 participants had T2DM and 63 had severe COVID-19. For 1780 previously published COVID-19-associated variants, 3 SNPs in the pre-imputation data and 23 SNPS in the imputed data were significantly associated with severe COVID-19 cases compared to controls (p<0.05). For 2755 published T2DM associated variants, 69 SNPs in the pre-imputation data and 419 SNPs in the imputed data were significantly associated with T2DM cases when compared to controls (p<0.05). Conclusions The results shown here are illustrative of what will be possible as the cohort expands in the future. Here we demonstrate the feasibility of this approach, recognising that the findings presented here are preliminary and require further validation once we have a sufficient sample size to improve statistical significance of findings. We implemented a genotyped population cohort with virtual follow up data in a resource-constrained African environment, demonstrating feasibility for scale up and novel health discoveries through nested case-control studies.https://wellcomeopenresearch.org/articles/9-620/v2Electronic routine health data virtual cohorts African genetic data H3Africa Illumina micro-array genotype data tiered informed consenteng |
| spellingShingle | Robert J Wilkinson Francisco Lakay Nicki Tiffin Joel A Dave Catherine Riou Peter Raubenheimer Anna K Coussens Tsaone Tamuhla Melissa J Blumenthal Maleeka Abrahams Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations] Wellcome Open Research Electronic routine health data virtual cohorts African genetic data H3Africa Illumina micro-array genotype data tiered informed consent eng |
| title | Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_full | Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_fullStr | Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_full_unstemmed | Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_short | Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_sort | implementation of a genotyped african population cohort with virtual follow up a feasibility study in the western cape province south africa version 2 peer review 2 approved 1 approved with reservations |
| topic | Electronic routine health data virtual cohorts African genetic data H3Africa Illumina micro-array genotype data tiered informed consent eng |
| url | https://wellcomeopenresearch.org/articles/9-620/v2 |
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