ArticleGenome biology2018
Genetic disease risks can be misestimated across global populations.
Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 3 of them syntheses that pooled it.
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Who cites it
122 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Polygenicity of Comorbid Depression in Multiple Sclerosis.Neurology · 2023Pooled it
- Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes.International journal of molecular sciences · 2020Pooled it
- Risk Prediction Models for Colorectal Cancer Incorporating Common Genetic Variants: A Systematic Review.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Pooled it
- 3D multi-omics tumour atlases: from technology to biology and clinical translation.Nature reviews. Cancer · 2026Review
- Associations of polygenic risk scores for type 2 diabetes with metabolic measures in Pacific Islanders from Guam and Saipan.Journal of human genetics · 2026Article
- Ancestry-Calibrated Polygenic Risk Scores Predict PTSD Trajectories in Recent Trauma Survivors and Interact with Neighborhood Resources.medRxiv : the preprint server for health sciences · 2026Article
- The Genetic and Transcriptomic Nexus of Age-Related Hearing Loss and Alzheimer's Disease.Genes · 2026Article
- Article
- Quantifying the utility of type 2 diabetes polygenic risk score for predicting incident diabetes: an analysis of large US-based cohort studies.BMC medical genomics · 2026Article
- Genetic predisposition for depression, psychosocial and behavioural factors and premenstrual symptoms: a cross-sectional study among young women in China.BMC medicine · 2026Article
- An integrative association analysis for complex diseases in underrepresented groups by leveraging the trans-ethnic genetic similarity.Briefings in bioinformatics · 2026Article
- Review
- Determining the driving factors shaping genetic architecture of complex traits in recently admixed populations.bioRxiv : the preprint server for biology · 2025Article
- Polygenic prediction of human complex traits using ancient DNA.Current opinion in genetics & development · 2025Review
- Bioinformatic analysis of rare endothelial protein C receptor missense variants associated with coagulation and thrombophilia risk.Scientific reports · 2025Article
- Causal Analyses of Associations Between Brain Structure and Suicide Attempt in Adulthood and Late Childhood.JAACAP open · 2025Article
- Methodological opportunities in genomic data analysis to advance health equity.Nature reviews. Genetics · 2025Review
- Characterization of the complex TB pharmacogenomic landscape in Africa using bioinformatic tools.Briefings in bioinformatics · 2025Article
- CADET: Enhanced transcriptome-wide association analyses in admixed samples using eQTL summary data.American journal of human genetics · 2025Article
- Development and Validation of Polygenic Risk Scores for Blood Pressure Traits in Continental African Populations.Circulation. Genomic and precision medicine · 2025Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundAccurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of genome-wide association studies (GWAS), and extensive computer simulations to identify how genetic disease risks can be misestimated.
resultsIn contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. Strikingly, ancestral risk alleles are found at 9.51% higher frequency in Africa, and derived risk alleles are found at 5.40% lower frequency in Africa. By simulating GWAS with different study populations, we find that non-African cohorts yield disease associations that have biased allele frequencies and that African cohorts yield disease associations that are relatively free of bias. We also find empirical evidence that genotyping arrays and SNP ascertainment bias contribute to continental differences in risk allele frequencies. Because of these causes, polygenic risk scores can be grossly misestimated for individuals of African descent. Importantly, continental differences in risk allele frequencies are only moderately reduced if GWAS use whole genome sequences and hundreds of thousands of cases and controls. Finally, comparisons between uncorrected and corrected genetic risk scores reveal the benefits of considering whether risk alleles are ancestral or derived.
conclusionsOur results imply that caution must be taken when extrapolating GWAS results from one population to predict disease risks in another population.
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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 Socratic graph.