ArticleGenome biology2022
Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.
Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Prostate cancer metastasis and health disparities: a systematic review.Prostate cancer and prostatic diseases · 2024Pooled it
- Mapping long-read sequences to a complete reference genome reveals uncaptured variants across the β-Globin cluster in Africans with sickle cell disease.HGG advances · 2026Article
- Precision Phenotyping With Audiometric Data and Gene Discovery for Sensorineural Hearing Loss.JAMA otolaryngology-- head & neck surgery · 2026Article
- Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.Molecular psychiatry · 2025Article
- Driving Global Health equity and precision medicine through African genomic data.Human molecular genetics · 2025Article
- Equitable machine learning counteracts ancestral bias in precision medicine.Nature communications · 2025Article
- Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations.medRxiv : the preprint server for health sciences · 2024Article
- The Geneticization of Education and Its Bioethical Implications.Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees · 2024Article
- Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.Nature genetics · 2024Article
- Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa.Nature genetics · 2024Article
- Multiancestry transferability of a polygenic risk score for diverticulitis.BMJ open gastroenterology · 2024Article
- Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.medRxiv : the preprint server for health sciences · 2024Article
- Protective alleles and precision healthcare in crewed spaceflight.Nature communications · 2024Review
- Imputation accuracy across global human populations.American journal of human genetics · 2024Article
- Parkinson Disease Genetics Extended to African and Hispanic Ancestries in the VA Million Veteran Program.Neurology. Genetics · 2024Article
- Principles and methods for transferring polygenic risk scores across global populations.Nature reviews. Genetics · 2024Review
- Preliminary effects of risk-adapted PSA screening for prostate cancer after integrating PRS-specific and age-specific variation.Frontiers in genetics · 2024Article
- Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Article
- Imputation Accuracy Across Global Human Populations.bioRxiv : the preprint server for biology · 2023Article
- Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.Research square · 2023Article
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Authors and funding
48 authors at 18 institutions in 6 countries.
Funding
Abstract
backgroundGenome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa.
resultsAllele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores.
conclusionsGenetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.
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