Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa.

Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Seeking support through solidarity: female leader's experiences of workplace solidarity in male-dominated professions.

Introduction: While there is a plethora of research that documents the numerous barriers affecting female leaders in the modern workplace, there is a lack of literature which focuses on strategies or motivating resources that women use to navigate the workplace environment. Despite facing significant barriers in their leadership journeys, there are female leaders who are able to overcome these barriers to achieve leadership positions. These women leaders draw on personal and external motivating factors to assist them in dealing with the challenges associated with being a female leader as a result, research on motivating strategies for women's career progression is a research topic that warrants immediate attention. Female solidarity as a motivating resource has been gaining traction in the field of leadership studies and can be seen as a supportive resource that can be used by current and aspiring female leaders to progress in underrepresented environments. Although female solidarity is but only one of the many strategies that can be implemented to motivate women in leadership positions, the increase of female solidarity in the workplace is expected to alleviate the conditions that reinforce essentialist notions of the "queen bee syndrome" in which women are seen as unsupportive of each other. Method: A qualitative research approach was used for this study, following an interpretive descriptive design. A total of 13 semi-structured interviews were conducted with female leaders in male-dominated professions within South Africa. Data was analysed using thematic content analysis. Results: Results of the study were analyzed in line with three primary content areas, i.e., barriers to female solidarity in the workplace, benefits of female solidarity in the workplace and workplace interventions to increase solidarity. Discussion: In the context of the study the predominant barriers to female solidarity within male-dominated workplaces were identified as unfair workplace behaviours, generational beliefs, societal expectations, organisational cultures, stereotypes and stigmas. The benefits of female solidarity within male-dominated workplaces were identified as career shaping mentorship, female recognition, female representation and female support. Lastly, the interventions that can be implemented to increase female solidarity within male-dominated workplaces were conceptualised as networking, transforming the company culture, socialisation and mentorship.

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

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.