On cross-ancestry cancer polygenic risk scores.

Polygenic risk scores (PRS) can provide useful information for personalized risk stratification and disease risk assessment, especially when combined with non-genetic risk factors. However, their construction depends on the availability of summary statistics from genome-wide association studies (GWA...

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Autores principales:	Lars G Fritsche, Ying Ma, Daiwei Zhang, Maxwell Salvatore, Seunggeun Lee, Xiang Zhou, Bhramar Mukherjee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/ce5c41751bd6496e9088c610675b838f
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spelling	oai:doaj.org-article:ce5c41751bd6496e9088c610675b838f2021-12-02T20:03:02ZOn cross-ancestry cancer polygenic risk scores.1553-73901553-740410.1371/journal.pgen.1009670https://doaj.org/article/ce5c41751bd6496e9088c610675b838f2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009670https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Polygenic risk scores (PRS) can provide useful information for personalized risk stratification and disease risk assessment, especially when combined with non-genetic risk factors. However, their construction depends on the availability of summary statistics from genome-wide association studies (GWAS) independent from the target sample. For best compatibility, it was reported that GWAS and the target sample should match in terms of ancestries. Yet, GWAS, especially in the field of cancer, often lack diversity and are predominated by European ancestry. This bias is a limiting factor in PRS research. By using electronic health records and genetic data from the UK Biobank, we contrast the utility of breast and prostate cancer PRS derived from external European-ancestry-based GWAS across African, East Asian, European, and South Asian ancestry groups. We highlight differences in the PRS distributions of these groups that are amplified when PRS methods condense hundreds of thousands of variants into a single score. While European-GWAS-derived PRS were not directly transferrable across ancestries on an absolute scale, we establish their predictive potential when considering them separately within each group. For example, the top 10% of the breast cancer PRS distributions within each ancestry group each revealed significant enrichments of breast cancer cases compared to the bottom 90% (odds ratio of 2.81 [95%CI: 2.69,2.93] in European, 2.88 [1.85, 4.48] in African, 2.60 [1.25, 5.40] in East Asian, and 2.33 [1.55, 3.51] in South Asian individuals). Our findings highlight a compromise solution for PRS research to compensate for the lack of diversity in well-powered European GWAS efforts while recruitment of diverse participants in the field catches up.Lars G FritscheYing MaDaiwei ZhangMaxwell SalvatoreSeunggeun LeeXiang ZhouBhramar MukherjeePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009670 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Lars G Fritsche Ying Ma Daiwei Zhang Maxwell Salvatore Seunggeun Lee Xiang Zhou Bhramar Mukherjee On cross-ancestry cancer polygenic risk scores.
description	Polygenic risk scores (PRS) can provide useful information for personalized risk stratification and disease risk assessment, especially when combined with non-genetic risk factors. However, their construction depends on the availability of summary statistics from genome-wide association studies (GWAS) independent from the target sample. For best compatibility, it was reported that GWAS and the target sample should match in terms of ancestries. Yet, GWAS, especially in the field of cancer, often lack diversity and are predominated by European ancestry. This bias is a limiting factor in PRS research. By using electronic health records and genetic data from the UK Biobank, we contrast the utility of breast and prostate cancer PRS derived from external European-ancestry-based GWAS across African, East Asian, European, and South Asian ancestry groups. We highlight differences in the PRS distributions of these groups that are amplified when PRS methods condense hundreds of thousands of variants into a single score. While European-GWAS-derived PRS were not directly transferrable across ancestries on an absolute scale, we establish their predictive potential when considering them separately within each group. For example, the top 10% of the breast cancer PRS distributions within each ancestry group each revealed significant enrichments of breast cancer cases compared to the bottom 90% (odds ratio of 2.81 [95%CI: 2.69,2.93] in European, 2.88 [1.85, 4.48] in African, 2.60 [1.25, 5.40] in East Asian, and 2.33 [1.55, 3.51] in South Asian individuals). Our findings highlight a compromise solution for PRS research to compensate for the lack of diversity in well-powered European GWAS efforts while recruitment of diverse participants in the field catches up.
format	article
author	Lars G Fritsche Ying Ma Daiwei Zhang Maxwell Salvatore Seunggeun Lee Xiang Zhou Bhramar Mukherjee
author_facet	Lars G Fritsche Ying Ma Daiwei Zhang Maxwell Salvatore Seunggeun Lee Xiang Zhou Bhramar Mukherjee
author_sort	Lars G Fritsche
title	On cross-ancestry cancer polygenic risk scores.
title_short	On cross-ancestry cancer polygenic risk scores.
title_full	On cross-ancestry cancer polygenic risk scores.
title_fullStr	On cross-ancestry cancer polygenic risk scores.
title_full_unstemmed	On cross-ancestry cancer polygenic risk scores.
title_sort	on cross-ancestry cancer polygenic risk scores.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ce5c41751bd6496e9088c610675b838f
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On cross-ancestry cancer polygenic risk scores.

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