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Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10(-6) and 10(-5) in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 × 10(-6); rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 × 10(-5)). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.

Background: The relationship between central adiposity and prostate cancer remains unclear., Methods: This report includes 963 newly diagnosed cases of histologically confirmed prostate cancer and 941 randomly selected age-matched controls ascertained from the population-based Prostate Cancer in a Black Population study conducted between July 2002 and January 2011 in Barbados, West Indies. Trained nurse interviewers obtained data on height, weight, waist and hip circumferences, family and medical history, and lifestyle factors. ORs and 95% confidence intervals (CI) were used to assess associations between anthropometric measures and prostate cancer., Results: A two-fold increased risk of prostate cancer was found among men in the highest quartile of waist-hip ratio compared with those in the lowest quartile (OR = 2.11, 95% CI, 1.54-2.88). Similarly, men with the largest waist circumferences had an OR of 1.84 (95% CI, 1.19-2.85) compared with those with the smallest waist sizes., Conclusions: These results suggest that measures of central rather than global adiposity may be more predictive of prostate cancer, especially in westernized African populations, where patterns of visceral fat distribution are different than other groups., Impact: The findings highlight the need to further elucidate the mechanisms underlying the relationship between central adiposity and prostate cancer in populations of predominantly African descent.

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.

Objective: To evaluate the prevalence of obesity and related sex-specific factors in a population of African descent., Design: Population-based cohort study., Setting and Participants: A simple random sample of 4,314 Barbados-born citizens of African origin, > or =40 years of age., Main Outcome Measure: Obesity was defined as a body mass index (BMI: kg/m2) > or =30., Results: A significant sex differential for obesity exists in this population, with 11.5% of men and 33.2% of women found to have a BMI > or =30. Factors such as hypertension, elevated glycosylated hemoglobin and nonprofessional education were positively associated with obesity in both men and women, whereas an inverse relationship was found between obesity, current smoking, and older age. Among males, current drinkers were more likely to be obese (OR = 1.43, 95% CI [1.04, 1.951), whereas the reverse pattern was observed in the females (OR = 0.59, [0.36, 0.981). Other factors associated with obesity, specifically related to women, included lower socioeconomic status and increased parity., Conclusions: The prevalence of obesity is high among Westernized women of African origin and cultural influences are thought to substantially contribute to this problem. Identifying sex-specific factors and providing culturally sensitive and tailored outreach services to those at highest risk may help to reduce the burden that obesity and its related comorbidities have placed on public healthcare systems worldwide.

Objective: To evaluate the prevalence, distribution, awareness, treatment and control of hypertension in an Afro-Caribbean population, and their relationship to 4-year survival. DESIGN Population-based prospective cohort study., Setting and Participants: Simple random sample of Barbados-born citizens (4709 persons; 84% participation), with 4-year follow-up., Interventions: None., Main Outcome Measures: Hypertension prevalence, awareness, treatment and control were evaluated at baseline. Four-year cumulative mortality was assessed by the product-limit method and relative risk of mortality by the Cox proportional hazards method., Results: Mean systolic (SBP) and diastolic (DBP) blood pressure were higher among black than white participants. In the black population, age-specific prevalence of hypertension increased from 32.7% in men and 34.0% in women at 40-49 years of age to 63.4% in men and 85.5% in women at ages 80 years and older, with an overall prevalence of 55.4%. Hypertension awareness, treatment and control rates were 62.5, 53.8 and 18.5%, respectively. Compared to DBP 80 mmHg, the presence of a DBP between 80 and 84 mmHg, 100-109 mmHg and > or = 110 mmHg was associated with adjusted death rate ratios of 1.6, 1.7 and 2.0, respectively. Systolic blood pressure was not related to the risk of cardiovascular mortality, after adjustment for age or other potential confounders. Hypertensives were at modestly increased risk of 4-year cardiovascular mortality [RR = 1.4; 95% confidence inteval (CI) (1.0, 2.0)], while treated uncontrolled hypertensives were at increased risk of all cause [RR = 1.4; 95% CI (1.0, 1.9)] and cardiovascular [RR = 1.6; 95% CI (1.1, 2.5)] mortality., Conclusions: High rates of hypertension in this population coexist with conservative levels of treatment and low rates of blood pressure control. In contrast to other reports, elevated SBP was not independently associated with increased risk of cardiovascular mortality. The modest impact of elevated blood pressure might partly explain the comparatively lower hypertension-related mortality rates in populations of Caribbean-origin. Treated uncontrolled hypertensives are at increased risk of early mortality, signaling the need for strict blood pressure control in this group.