A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa.
Black People
/ genetics
Case-Control Studies
Cohort Studies
Genetic Loci
Genetic Predisposition to Disease
Genetics, Population
Genome-Wide Association Study
Humans
Male
Neoplasms
/ classification
Polymorphism, Single Nucleotide
Prostatic Neoplasms
/ classification
Risk Factors
South Africa
/ epidemiology
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
15
07
2019
revised:
03
10
2019
accepted:
06
05
2020
pubmed:
13
5
2020
medline:
18
11
2020
entrez:
13
5
2020
Statut:
ppublish
Résumé
Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. SIGNIFICANCE: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.
Identifiants
pubmed: 32393663
pii: 0008-5472.CAN-19-2165
doi: 10.1158/0008-5472.CAN-19-2165
pmc: PMC7335354
mid: NIHMS1594370
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2956-2966Subventions
Organisme : NCI NIH HHS
ID : R01 CA256058
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA184374
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007590
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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