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Variability of poly...
Variability of polygenic prediction for body mass index in Africa
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- Chikowore, Tinashe (author)
- Harvard Medical School,University of the Witwatersrand,Brigham and Women's Hospital / Harvard Medical School
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- Läll, Kristi (author)
- University of Tartu
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- Micklesfield, Lisa K. (author)
- University of the Witwatersrand
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- Lombard, Zane (author)
- University of the Witwatersrand
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- Goedecke, Julia H. (author)
- University of the Witwatersrand,South African Medical Research Council
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- Fatumo, Segun (author)
- Queen Mary University,MRC/UVRI Uganda Research Unit
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- Norris, Shane A. (author)
- University of Southampton,University of the Witwatersrand
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- Magi, Reedik (author)
- University of Tartu
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- Ramsay, Michele (author)
- University of the Witwatersrand
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- Franks, Paul W. (author)
- Lund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Harvard University
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- Pare, Guillaume (author)
- McMaster University
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- Morris, Andrew P. (author)
- University of Manchester
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Genome Medicine. - 1756-994X. ; 16:1
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http://dx.doi.org/10... (free)
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Abstract
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- Background: Polygenic prediction studies in continental Africans are scarce. Africa’s genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required. Methods: Using the first multi-ancestry genome-wide association study (GWAS) meta-analysis for BMI involving continental Africans, we derived a multi-ancestry PRS and compared its performance to a European ancestry-specific PRS in continental Africans (AWI-Gen study) and a European cohort (Estonian Biobank). We then evaluated the factors affecting the performance of the PRS in Africans which included fine-mapping resolution, allele frequencies, linkage disequilibrium patterns, and PRS-environment interactions. Results: Polygenic prediction of BMI in continental Africans is poor compared to that in European ancestry individuals. However, we show that the multi-ancestry PRS is more predictive than the European ancestry-specific PRS due to its improved fine-mapping resolution. We noted regional variation in polygenic prediction across Africa’s East, South, and West regions, which was driven by a complex interplay of the PRS with environmental factors, such as physical activity, smoking, alcohol intake, and socioeconomic status. Conclusions: Our findings highlight the role of gene-environment interactions in PRS prediction variability in Africa. PRS methods that correct for these interactions, coupled with the increased representation of Africans in GWAS, may improve PRS prediction in Africa.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- BMI
- Polygenic prediction
- Polygenic risk score
- Variability
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Chikowore, Tinas ...
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Läll, Kristi
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Micklesfield, Li ...
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Lombard, Zane
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Goedecke, Julia ...
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Fatumo, Segun
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Norris, Shane A.
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Magi, Reedik
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Ramsay, Michele
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Franks, Paul W.
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Pare, Guillaume
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Morris, Andrew P ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Genome Medicine
- By the university
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Lund University