Dataset Information

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

ABSTRACT:

Background

Genome-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.

Results

Allele 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.

Conclusions

Genetic 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.

SUBMITTER: Kim MS

PROVIDER: S-EPMC9472407 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

Kim Michelle S MS Naidoo Daphne D Hazra Ujani U Quiver Melanie H MH Chen Wenlong C WC Simonti Corinne N CN Kachambwa Paidamoyo P Harlemon Maxine M Agalliu Ilir I Baichoo Shakuntala S Fernandez Pedro P Hsing Ann W AW Jalloh Mohamed M Gueye Serigne M SM Niang Lamine L Diop Halimatou H Ndoye Medina M Snyper Nana Yaa NY Adusei Ben B Mensah James E JE Abrahams Afua O D AOD Biritwum Richard R Adjei Andrew A AA Adebiyi Akindele O AO Shittu Olayiwola O Ogunbiyi Olufemi O Adebayo Sikiru S Aisuodionoe-Shadrach Oseremen I OI Nwegbu Maxwell M MM Ajibola Hafees O HO Oluwole Olabode P OP Jamda Mustapha A MA Singh Elvira E Pentz Audrey A Joffe Maureen M Darst Burcu F BF Conti David V DV Haiman Christopher A CA Spies Petrus V PV van der Merwe André A Rohan Thomas E TE Jacobson Judith J Neugut Alfred I AI McBride Jo J Andrews Caroline C Petersen Lindsay N LN Rebbeck Timothy R TR Lachance Joseph J

Genome biology 20220913 1

<h4>Background</h4>Genome-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 fr ...[more]

PMID: 36100952

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Dataset Information

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

Background

Results

Conclusions

Publications

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

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