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Figure S1. Cross-validation error in ADMIXTURE analyses. The best fit to data occurs at K = 3.

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.

Successfully called markers on the MADCaP Array. This tab-delimited file includes genomic positions, inclusion criteria, and overlap with other arrays.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Background: There is a growing body of evidence supporting the contributions of germline rare variants to the susceptibility of prostate cancer (PCa), especially aggressive PCa. Our previous exome sequencing analysis highlighted 36 aggressive PCa candidate genes in populations of European ancestry. Here we investigated whether rare germline pathogenic, likely pathogenic, or deleterious (P/LD/D) variants in these genes were associated with overall and aggressive PCa risk in men of African ancestry. Methods: This exome sequencing analysis consists of 7,176 prostate cancer cases and 4,873 controls from the Research on Prostate Cancer in Men of African Ancestry (RESPOND) study. Among the PCa cases, 3,283 are aggressive cases (tumor stage T3/T4, regional lymph node involvement, metastatic disease, Gleason score >= 8.0, prostate-specific antigen [PSA] level >= 20 ng/mL or PCa as the underlying cause of death) including 1,074 metastatic cases, and 1,752 are non-aggressive cases (Gleason score ⇐ 7.0, PSA < 20 ng/mL, and tumor stage T1/T2). P/LP/D variants analyzed were rare (minor allele frequency < 1% in controls) and had either a Variant Effect Predictor impact score of “high” or a pathogenic or likely pathogenic ClinVar classification. The association between P/LP/D carrier status with risk of overall PCa, aggressive PCa, and metastatic PCa was evaluated in logistic regression models, adjusting for age and the top ten principal components. All statistical tests are two-sided. Results: Of the 36 PCa candidate genes, BRCA2 was the most frequently affected gene, with 1.7% of cases and 1.1% of controls harboring a germline P/LP/D variant, followed by MUTYH (1.5%/1.3%) ATM (0.93%/0.49%), MSH5 (0.70%/0.51%) and HOXB13 (0.70%/0.35%). Nominally significant associations with overall PCa were observed for ATM (OR=1.83, 95% CI=1.14-2.92, P=0.012), BRCA2 (OR=1.52, 95% CI=1.10-2.10, P=0.011), HOXB13 (OR=2.10, 95% CI=1.12-3.66, P=0.008), and PALB2 (OR=3.46, 95% CI=1.18-10.1, P=0.02). In case-case analyses (aggressive vs. non-aggressive cases), the association with aggressive PCa was nominally significant for ATM (OR=5.10, 95% CI=1.96-13.3, P=8.7 × 10−4) and BRCA2 (OR=2.00, 95% CI=1.19-3.38, P=0.009) and was suggestive for PALB2 (OR=2.99, 95% CI=0.83-10.7, P=0.09). Similar associations with metastatic PCa were also observed for these three genes. Conclusion: The associations of BRCA2, ATM, and PALB2 with overall PCa and aggressive PCa observed in men of African ancestry are consistent with findings from our previous study in men of European ancestry. These findings further support the importance of these genes in the consideration of screening and active surveillance for high-risk and advanced disease. Citation Format: Fei Chen, Burcu F. Darst, Xin Sheng, Anqi Wang, Yili Xu, Raymond Hughley, Ben Adusei, Mohamed Jalloh, Serigne Magueye Gueye, Andrew A. Adjei, James Mensah, Pedro W. Fernandez, Akindele O. Adebiyi, Oseremen Aisuodionoe-Shadrach, Lindsay Petersen, Maureen Joffe, Jo McBride, Jeannette T. Bensen, James L. Mohler, Jack A. Taylor, Eboneé N. Butler, Sue A. Ingles, Benjamin A. Rybicki, Janet L. Stanford, Wei Zheng, Sonja I. Berndt, Chad D. Huff, Joseph Lachance, Luc Multigner, Caroline Andrews, Timothy R. Rebbeck, Laurent Brureau, Stephen J. Chanock, David V. Conti, Christopher A. Haiman. Association of prostate cancer candidate genes with overall and aggressive prostate cancer in men of African ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1182.

Background:We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies.Methods:Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case–control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population.Results:The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90–100% of the PRS) to the average 40–60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62–3.96), 2.8-fold in African ancestry men (95% CI = 2.59–3.03), and 3.2-fold in Hispanic men (95% CI = 2.64–3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55–60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40–60% PRS category.Conclusions:Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection.Funding:This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

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.

Dementia is a chronic progressive disease that mostly affects the elderly. There is often a stigma surrounding dementia patients because of poor awareness about the disease. In Nigeria, this stigma and related attitudes have not been fully explored. In this study, we assessed the attitude of people towards demented individuals in a transitional community in Nigeria.The study used a mixed methods approach. Focused group discussions exploring the concept of dementia were conducted among six community groups, and quantitative data was obtained from an interviewer-administered questionnaire. A total of 313 respondents were selected with a cluster sampling technique.Only 212 respondents (67.7%) were aware of dementia. 'Memory loss disease', 'ageing disease', 'disease of insanity', 'brain disorder', 'disease of forgetfulness', and 'dull brain' are the common names used to describe dementia in the community. Enacted stigma was evident as 36% of respondents felt dementia was associated with shame and embarrassment in the community. Implied stigma was evident in another third that opined that demented individuals would prefer not to know or let others know that they have the disease. Also, 28% were of the opinion that people do not take those with dementia seriously. Of the 22 (10.4%) that reported having received structured information about dementia, 16 (72.7%) got the information from health facilities. Qualitative data revealed the presence of enacted stigma in the community as some referred to affected individuals by derogatory names such as 'madman'. Some statements from the focus group discussion participants also gave useful insights into the scorn with which demented individuals are sometimes treated.The presence of enacted and implied stigma related to dementia within the community calls for concern. More research efforts are needed to unravel the burden of stigma within communities and best practice for stigma-reducing interventions.

This pilot was conducted to determine the incidence and forms of electronic-media harassment among secondary school students. Students who owned a mobile phone and had access to the Internet were selected via multi-stage sampling. History of harassment in the 3-month period preceding the study was obtained. Results A total of 129 students- 65(52.4%) boys and 59(47.6%) girls with mean age of 13.9(±1.9) years participated. Eighty-four(66.1%) were from private and 43(33.9%) government-owned schools; 65(51.2%) were in junior and 62(48.8%) in senior classes; 88.2% lived with both parents. All respondents had personal phones and 66(52.0%) had access to the Internet. Forty-three (33.9%) had suffered electronic harassment while 19(15.0%) had harassed others. Twenty-four (18.9%) were victims only, all 19(15%) perpetrators were also victims. The commonest modes of harassment were text messages 31(24.4%) and phone calls 25(19.5%). Of the 66 with Internet access, four each had experienced harassment through email and in chat rooms and two via websites. Twenty-one (16.5%) had harassed others via text messages, 21(16.5%) through phone calls and 6(4.7%) through picture or video clips. Perpetrators were mainly boys. The incident was often reported to friends, parents/guardians, other adults in school, class teachers. Factors predictive of being a victim were public schooling(OR 4.9, 95%CI 2.0 to 11.9), and being in a senior class(OR 3.5, 95% CI 1.6 to 8.6). Conclusion This pilot revealed that electronic media harassment was occurring among the students. This phenomenon thus needs to be further investigated and efforts put in place to curb it.

Introduction In an unsafe environment, youths are denied the opportunity to develop psychosocially, and intellectually. This study sought to find out the perception of senior in-school youths about community and school safety. Methodology Cross sectional study of senior in-school youths was carried out using a total sample of consenting students. A self administered questionnaire was used to elicit information on socio-demographic characteristics, perception of and characteristics of safe communities and schools. Results The mean age of respondents was 16.41.6 years and 54.7% were females. Majority (62.4%) live in densely populated area. Only 182 (50.0%) perceived their school to be safe, 154 (42.3%) perceived it to be unsafe and 28 (7.7%) couldn9t make up their minds. However, 265 (72.8%) reported their communities as safe, 66 (18.1%) as unsafe and 33 (9.1%) had no opinion. The most important perceived feature of a safe community mentioned was security 209 (57.4%) and 22.5% of youths have ever been molested. Within 6 months preceding study, 50 (13.7%) had felt unsafe and those reporting incidents like rape, street robbery, drug use and youth gangs as occurrences in their communities were 111 (30.5%), 127 (34.9%), 167 (45.9%), 151 (41.5%) respectively. Street lights, Zebra crossings and side-walks were absent in 81%, 83.8% and 56.9% of the communities respectively. Conclusion More youths perceived their schools to be unsafe. The prevalence of drug use and youth gangs was quite high in neighbourhoods. Further researches on school safety are desirable while governments and communities should begin to collaborate on safety issues.