CDKN2B Polymorphism Is Associated with Primary Open-Angle Glaucoma (POAG) in the Afro-Caribbean Population of Barbados, West Indies

The purpose of this study was to confirm previously reported associations of common variants in or near CDC7/TGFBR3, ZP4, SRBD1, ELOVL5, CAV1/CAV2, TLR4, CDKN2B, CDKN2B-AS1, ATOH7, PLXDC2, TMTC2, SIX1, and CARD10, with primary open angle glaucoma (POAG) in the Afro-Caribbean population of Barbados, West Indies. A total of 437 unrelated subjects from the Barbados Family Study of Open Angle Glaucoma (BFSG), including 272 with POAG and 165 unaffected individuals were included in this study. Eighteen SNPs were genotyped by using the multiplex SNaPshot method. Allelic, genotypic and model-based (dominant, recessive, and additive) associations of the SNPs with POAG were analyzed using Chi-squared tests and logistic regression. SNP rs1063192 (near CDKN2B) was found to be significantly associated with POAG (allelic P = 0.0008, genotypic P = 0.0029), and the minor allele C of rs1063192 was protective against POAG (OR  = 0.39; 95%CI  = 0.22−0.69). Suggestive association was also noted for rs7916697 (near ATHO7, allelic P  = 0.0096, genotypic P = 0.01) with the minor allele being protective (OR  = 0.67; 95% CI  = 0.50−0.91), although this finding did not withstand correction for multiple testing. However, a significant interactive effect on POAG risk was identified between rs1063192 and rs7916697 (P-interaction  = 2.80×10−5). Individuals with the rs1063192 protective genotype CC or CT and also rs7916697 genotypes GG or GA show a significantly decreased risk of POAG (OR = 0.17, 95%CI: 0.07−0.41). Our study confirms the significant association between SNP rs1063192 (CDKN2B, previously shown to influence vertical cup-to-disc ratio and POAG at 9p21) and POAG in the Afro-Caribbean population of Barbados. The minor allele of rs1063192 interacts with that of rs7916697 (ATOH7)) to reduce POAG risk. Our results also suggest that rs1063912 is a common protective variant for POAG in populations of African as well as European descent

Prostate Cancer Incidence and Mortality in Barbados, West Indies

We describe prostate cancer incidence and mortality in Barbados, West Indies. We ascertained all histologically confirmed cases of prostate cancer during the period July 2002 to December 2008 and reviewed each death registration citing prostate cancer over a 14-year period commencing January 1995. There were 1101 new cases for an incidence rate of 160.4 (95% Confidence Interval: 151.0–170.2) per 100,000 standardized to the US population. Comparable rates in African-American and White American men were 248.2 (95% CI: 246.0–250.5) and 158.0 (95% CI: 157.5–158.6) per 100,000, respectively. Prostate cancer mortality rates in Barbados ranged from 63.2 to 101.6 per 100,000, compared to 51.1 to 78.8 per 100,000 among African Americans. Prostate cancer risks are lower in Caribbean-origin populations than previously believed, while mortality rates appeared to be higher than reported in African-American men. Studies in Caribbean populations may assist understanding of disparities among African-origin populations with shared heredity

Comparison of the Systemic Lupus Erythematosus Activity Questionnaire and the Systemic Lupus Erythematosus Disease Activity Index in a Black Barbadian Population

In Barbados, use of the Systemic Lupus Erythematosus (SLE) Disease Activity Index (SLEDAI) is limited by the unavailability of serologic markers. The SLE Activity Questionnaire (SLAQ) excludes laboratory measurements and is therefore more accessible. Here, we investigate the agreement between the SLAQ, the SLEDAI, and the physician global assessment (PGA). A pilot of 32 participants completed the SLAQ and SLEDAI. The tools were compared (1) in their original format, (2) limited to common indices, and (3) limited to the same patient recall period. We compared the proportions of persons reporting disease activity and the concordance between calculated activity scores for SLAQ versus SLEDAI and for SLAQ versus PGA. Seventy-eight percent versus 59% of participants reported disease activity with the original SLEDAI versus SLAQ, respectively. The relationship was reversed to 22% versus 59% when the matched item tools were compared. Concordance was 0.62 (95% CI 0.42-0.81) between the original scores, 0.70 (0.57-0.83) when restricted by matched items, and 0.72 (0.59-0.84) when further restricted by recall period. Concordance between the SLAQ and PGA was 0.56 (0.32-0.80). Reversal of the disease activity percentage in the matched items comparison highlights the inadequacy of tools that exclude laboratory measurements and suggests that the subjective nature of SLAQ may contribute to over-reporting. Further work is needed to produce a robust disease activity tool apt for resourceconstrained environments

Sodium and potassium excretion in an adult Caribbean population of African descent with a high burden of cardiovascular disease

Abstract Background High sodium diets with inadequate potassium and high sodium-to-potassium ratios are a known determinant of hypertension and cardiovascular disease (CVD). The Caribbean island of Barbados has a high prevalence of hypertension and mortality from CVD. Our objectives were to estimate sodium and potassium excretion, to compare estimated levels with recommended intakes and to identify the main food sources of sodium in Barbadian adults. Methods A sub-sample (n = 364; 25–64 years) was randomly selected from the representative population-based Health of the Nation cross-sectional study (n = 1234), in 2012–13. A single 24-h urine sample was collected from each participant, following a strictly applied protocol designed to reject incomplete samples, for the measurement of sodium and potassium excretion (in mg), which were used as proxy estimates of dietary intake. In addition, sensitivity analyses based on estimated completeness of urine collection from urine creatinine values were undertaken. Multiple linear regression was used to examine differences in sodium and potassium excretion, and the sodium-to-potassium ratio, by age, sex and educational level. Two 24-h recalls were used to identify the main dietary sources of sodium. All analyses were weighted for the survey design. Results Mean sodium excretion was 2656 (2488–2824) mg/day, with 67% (62–73%) exceeding the World Health Organization (WHO) recommended limit of 2000 mg/d. Mean potassium excretion was 1469 (1395–1542) mg/d; < 0.5% met recommended minimum intake levels. Mean sodium-to-potassium ratio was 2.0 (1.9–2.1); not one participant had a ratio that met WHO recommendations. Higher potassium intake and lower sodium-to-potassium ratio were independently associated with age and tertiary education. Sensitivity analyses based on urine creatinine values did not notably alter these findings. Conclusions In this first nationally representative study with objective assessment of sodium and potassium excretion in a Caribbean population in over 20 years, levels of sodium intake were high, and potassium intake was low. Younger age and lower educational level were associated with the highest sodium-to-potassium ratios. These findings provide baseline values for planning future policy interventions for non-communicable disease prevention

Leveraging population admixture to characterize the heritability of complex traits.

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)

Derivation, internal validation, and recalibration of a cardiovascular risk score for Latin America and the Caribbean (Globorisk-LAC): A pooled analysis of cohort studies

Background Risk stratification is a cornerstone of cardiovascular disease (CVD) prevention and a main strategy proposed to achieve global goals of reducing premature CVD deaths. There are no cardiovascular risk scores based on data from Latin America and the Caribbean (LAC) and it is unknown how well risk scores based on European and North American cohorts represent true risk among LAC populations. Methods We developed a CVD (including coronary heart disease and stroke) risk score for fatal/non-fatal events using pooled data from 9 prospective cohorts with 21,378 participants and 1,202 events. We developed laboratory-based (systolic blood pressure, total cholesterol, diabetes, and smoking), and office-based (body mass index replaced total cholesterol and diabetes) models. We used Cox proportional hazards and held back a subset of participants to internally validate our models by estimating Harrell's C-statistic and calibration slopes. Findings The C-statistic for the laboratory-based model was 72% (70–74%), the calibration slope was 0.994 (0.934–1.055) among men and 0.852 (0.761–0.942) among women; for the office-based model the C-statistic was 71% (69–72%) and the calibration slope was 1.028 (0.980–1.076) among men and 0.811 (0.663–0.958) among women. In the pooled sample, using a 20% risk threshold, the laboratory-based model had sensitivity of 21.9% and specificity of 94.2%. Lowering the threshold to 10% increased sensitivity to 52.3% and reduced specificity to 78.7%. Interpretation The cardiovascular risk score herein developed had adequate discrimination and calibration. The Globorisk-LAC would be more appropriate for LAC than the current global or regional risk scores. This work provides a tool to strengthen risk-based cardiovascular prevention in LAC

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry

Sex and the city: Differences in disease- and disability-free life years, and active community participation of elderly men and women in 7 cities in Latin America and the Caribbean

<p>Abstract</p> <p>Background</p> <p>The world's population is ageing, and four of the top 10 most rapidly ageing developing nations are from the region of Latin America and the Caribbean (LAC).</p> <p>Although an ageing population heralds likely increases in chronic disease, disability-related dependence, and economic burden, the societal contribution of the chronically ill or those with disability is not often measured.</p> <p>Methods</p> <p>We calculated country-specific prevalences of 'disability' (difficulty with at least one activity of daily living), 'disease' and 'co-morbidity' (presence of at least one, and at least two, of seven chronic diseases/conditions, respectively), and 'active community engagement' (using five levels of community participation, from less than weekly community contact to voluntary or paid work) in seven LAC cities. We estimated remaining life expectancy (LE) with and without disability, disease and co-morbidity, and investigated age, sex, and regional variations in disability-free LE. Finally, we modeled the association of disease, co-morbidity and disability with active community participation using an ordinal regression model, adjusted for depression.</p> <p>Results</p> <p>Overall, 77% of the LAC elderly had at least one chronic disease/condition, 44% had co-morbidity and 19% had a disability. The proportion of disability-free LE declined between the youngest (60–64 years) and the eldest (90 years and over) age-groups for both men (from 85% to 55%) and women (from 75% to 45%). Disease-free and co-morbidity-free LE, however, remained at approximately 30% and 62%, respectively, for men (20% and 48% for women), until 80–84 years of age, then increased. Only Bridgetown's participants had statistically significantly longer disability-free LE than the regional average (IRR = 1.08; 95%CI 1.05–1.10; p < 0.001). Only Santiago's participants had disability-free LE which was shorter than the regional average (IRR = 0.94; 95%CI 0.92–0.97; p < 0.001). There was 75% active community participation overall, with more women than men involved in active help (49% vs 32%, respectively) and more men involved in voluntary/paid work (46% vs 25%, respectively). There was either no, or borderline significance in the association between having one or more diseases/conditions and active community engagement for both sexes. These associations were limited by depression (odds ratio [OR] reduced by 15–17% for men, and by 8–11% for women), and only remained statistically significant in men. However, disability remained statistically significantly associated with less community engagement after adjusting for depression (OR = 0.58, 95%CI 0.49–0.69, p < 0.001 for women and OR = 0.50, 95%CI 0.47–0.65, p < 0.001 for men).</p> <p>Conclusion</p> <p>There is an increasing burden of disease and disability with older age across the LAC region. As these nations cope with resulting social and economic demands, governments and civic societies must continue to develop and maintain opportunities for community participation by this increasingly frail, but actively engaged group.</p

Cohort profile: The Cohorts Consortium of Latin America and the Caribbean (CC-LAC)

Why was the cohort set up? Latin America and the Caribbean (LAC) are characterized by much diversity in terms of socio-economic status, ecology, environment, access to health care,1,2 as well as the frequency of risk factors for and prevalence or incidence of non-communicable diseases;3–7 importantly, these differences are observed both between and within countries in LAC.8,9 LAC countries share a large burden of non-communicable (e.g. diabetes and hypertension) and cardiovascular (e.g. ischaemic heart disease) diseases, with these conditions standing as the leading causes of morbidity, disability and mortality in most of LAC.10–12 These epidemiological estimates—e.g. morbidity—cannot inform about risk factors or risk prediction, which are relevant to identify prevention avenues. Cohort studies, on the other hand, could provide this evidence. Pooled analysis, using data from multiple cohort studies, have additional strengths such as increased statistical power and decreased statistical uncertainty.13 LAC cohort studies have been under-represented,14 or not included at all,15–17 in international efforts aimed at pooling data from multiple cohort studies. We therefore set out to pool data from LAC cohorts to address research questions that individual cohort studies would not be able to answer. Drawing from previous successful regional enterprises (e.g. Asia Pacific Cohort Studies Collaboration),18,19 we established the Cohorts Consortium of Latin America and the Caribbean (CC-LAC). The main aim of the CC-LAC is to start a collaborative cohort data pooling in LAC to examine the association between cardio-metabolic risk factors (e.g. blood pressure, glucose and lipids) and non-fatal and fatal cardiovascular outcomes (e.g. stroke or myocardial infarction). In so doing, we aim to provide regional risk estimates to inform disease burden metrics, as well as other ambitious projects including a cardiovascular risk score to strengthen cardiovascular prevention in LAC. Initial funding has been provided by a fellowship from the Wellcome Trust Centre for Global Health Research at Imperial College London (Strategic Award, Wellcome Trust–Imperial College Centre for Global Health Research, 100693/Z/12/Z). Additional funding is being provided by an International Training Fellowship from the Wellcome Trust (214185/Z/18/Z). At the time of writing, the daily operations and pooled database are hosted at Imperial College London, though a mid-term goal is to transfer this expertise and operations to LAC. The collaboration relies fundamentally on a strong regional network of health researchers and practitioner