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Variability of polygenic prediction for body mass index in Africa

Chikowore, Tinashe ; Läll, Kristi ; Micklesfield, Lisa K. ; Lombard, Zane ; Goedecke, Julia H. ; Fatumo, Segun ; Norris, Shane A. ; Magi, Reedik ; Ramsay, Michele and Franks, Paul W. LU , et al. (2024) In Genome Medicine 16(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BMI, Polygenic prediction, Polygenic risk score, Variability
in
Genome Medicine
volume
16
issue
1
article number
74
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85194775287
  • pmid:38816834
ISSN
1756-994X
DOI
10.1186/s13073-024-01348-x
language
English
LU publication?
yes
id
706a5bd5-df29-42ee-917a-f542c91bbaef
date added to LUP
2024-08-23 15:16:14
date last changed
2024-08-28 14:17:05
@article{706a5bd5-df29-42ee-917a-f542c91bbaef,
  abstract     = {{<p>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.</p>}},
  author       = {{Chikowore, Tinashe and Läll, Kristi and Micklesfield, Lisa K. and Lombard, Zane and Goedecke, Julia H. and Fatumo, Segun and Norris, Shane A. and Magi, Reedik and Ramsay, Michele and Franks, Paul W. and Pare, Guillaume and Morris, Andrew P.}},
  issn         = {{1756-994X}},
  keywords     = {{BMI; Polygenic prediction; Polygenic risk score; Variability}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Genome Medicine}},
  title        = {{Variability of polygenic prediction for body mass index in Africa}},
  url          = {{http://dx.doi.org/10.1186/s13073-024-01348-x}},
  doi          = {{10.1186/s13073-024-01348-x}},
  volume       = {{16}},
  year         = {{2024}},
}