Heterogeneity in polygenic scores for common human traits
Open accessAbstract
Genome-wide association studies (GWAS) on a wide range of important human traits have identified hundreds of variants in multi-cohort meta-analyses that have highly significant associations (p<5 x10-8) that replicate across studies. However, the identified genetic variants, or single nucleotide
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PRS are many-fold more accurate in European ancestry individuals than in others, and this disparity is the major ethical and scientific challenge surrounding clinical implementation.
“However, the major ethical and scientific challenge surrounding clinical implementation is that they are many-fold more accurate in European ancestry individuals than others.”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [16]
The Discussion reports that European-ancestry-weighted scores explained approximately twice as much trait variation in the HRS non-Hispanic White sample as in the non-Hispanic Black sample. That supports a performance disparity, but not a general claim about all other ancestries or that the scores are “many-fold more accurate.” The paper does not identify this disparity as the major ethical and scientific challenge to clinical implementation. (LLM, conf=0.89)
Experimental — accuracy not yet measuredThe scientific basis of the imbalance in PRS accuracy has been demonstrated theoretically, in simulations, and empirically across many traits and diseases.
“The scientific basis of this imbalance has been demonstrated theoretically, in simulations, and empirically across many traits and diseases11–22.”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [16]
The Cross-race/ethnicity comparison and Discussion (pages not provided) report empirical differences in polygenic-score performance between non-Hispanic White and Black participants across the traits studied. The paper does not establish this imbalance theoretically or through simulations, and its empirical analysis is limited to four traits rather than many traits and diseases. (LLM, conf=0.87)
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Cites
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Clinical use of current polygenic risk scores may exacerbate health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2019) · Nature Genetics · doi:10.1038/s41588-019-0379-x · Cited by 2,831 · see citing works
Current clinical use of polygenic scores will risk exacerbating health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2018) · doi:10.1101/441261 · Cited by 2,813 · see citing works
Genomic prediction of depression risk and resilience under stress
Fang, Y., Scott, L., Song, P., Burmeister, M., & Sen, S. (2019) · Nature Human Behaviour · doi:10.1038/s41562-019-0759-3 · Cited by 43 · see citing works
Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course
van der Laan, C. M., Morosoli-García, J. J., van de Weijer, S. G. A., Colodro-Conde, L., the ACTION Consortium, Ip, H. F., van der Laan, C. M., Krapohl, E. M. L., Brikell, I., Sánchez-Mora, C., et al. (2021) · Behavior Genetics · doi:10.1007/s10519-021-10076-6 · Cited by 24 · see citing works
- Authors
- Ware, E. B., Schmitz, L. L., Faul, J., Gard, A., Mitchell, C., Smith, J. A., Zhao, W., Weir, D., & Kardia, S. L.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Ware, Erin B
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2017-02-05
- OpenAlex
- W2586927005
- Cited by
- 123
- References
- 3
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 12 · 2022: 16 · 2021: 18 · 2020: 24 · 2019: 30 · 2018: 13
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- polygenic risk score, heterogeneity, genetic variants, genome-wide association study, replication, polygenic risk
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