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Background: This study aimed to explore association of self-reported physical activity domains of work, leisure, and transport-related physical activity and body mass index (BMI) in 9388 adult men and women from the Africa-Wits-INDEPTH partnership for Genomic (AWI-Gen) study in Africa. Africa-Wits-INDEPTH partnership for Genomic is a large, population-based cross-sectional cohort with participants from 6 sites from rural and urban areas in 4 sub-Saharan African countries. Methods: A sex-stratified meta-analysis of cross-sectional data from men and women aged 29–82 years was used to assess the association of physical activity with BMI. Results: Overall, meeting physical activity guidelines of at least 150 minutes per week was associated with 0.82 kg/m2 lower BMI in men (β = −0.80 kg/m2; 95% confidence interval [CI], −1.14 to −0.47) and 0.68 kg/m2 lower BMI in women (β = −0.68 kg/m2; 95% CI, −1.03 to −0.33). Sex and site-specific differences were observed in the associations between physical activity domains and BMI. Among those who met physical activity guidelines, there was an inverse association between transport-related physical activity and BMI in men from Nanoro (Burkina Faso) (β = −0.79 kg/m2; 95% CI, −1.25 to −0.33) as well as work-related physical activity and BMI in Navrongo men (Ghana) (β = −0.76 kg/m2; 95% CI, −1.25 to −0.27) and Nanoro women (β = −0.90 kg/m2; 95% CI, −1.44 to −0.36). Conclusions: Physical activity may be an effective strategy to curb rising obesity in Africa. More studies are needed to assess the impact of sex and geographic location-specific physical activity interventions on obesity. [ABSTRACT FROM AUTHOR]

H3Africa is developing capacity for health-related genomics research in Africa

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub‐Saharan African (SSA) populations. We called star alleles from 961 high‐depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high‐coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21–47% and 2–19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0–6%, 3–10%, and 6–20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African‐ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single‐Molecule Real‐Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes—derived from activity scores—were examined across multiple sub‐Saharan African populations based on bioinformatics analysis of 961 high‐depth whole genome sequences. This was followed by characterization of novel star alleles and suballeles in a subset of the participants via targeted high‐fidelity Single‐Molecule Real‐Time resequencing (Pacific Biosciences). This study revealed varying frequencies of known CYP2D6 alleles and predicted phenotypes across different African ethnolinguistic groups. Twenty‐seven novel CYP2D6 star alleles were predicted computationally and two of them were further validated. This study highlights the importance of studying variation in key pharmacogenes such as CYP2D6 in the African context to better understand population‐specific allele frequencies. This will aid in the development of better genotyping panels and star allele detection approaches with a view toward supporting effective implementation of precision medicine strategies in Africa and across the African diaspora. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life's simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT).Methods: We conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status.Results: The mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 μm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (β-coefficients [95% confidence interval]: Burkina Faso, - 6.51 [- 9.83, - 3.20] μm; Ghana, - 5.42 [- 8.90, - 1.95]; Kenya, - 6.58 [- 9.05, - 4.10]; and South Africa, - 7.85 [- 9.65, - 6.05]). Inverse relations were observed for women (- 4.44 [- 6.23, - 2.65]) and men (- 6.27 [- 7.91, - 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001).Conclusion: This large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia. [ABSTRACT FROM AUTHOR]

Variations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have been performed in sub-Saharan Africans. This study evaluated the effect of single nucleotide variants (SNVs) in eight candidate loci (ABCA1 , LCAT , LPL , PON1 , CETP , PCSK9 , MVK , and MMAB) on lipid levels among 1855 Ghanaian adults. All lipid levels were measured directly using an automated analyser. DNA was extracted and genotyped using the H3Africa SNV array. Linear regression models were used to test the association between SNVs and log-transformed lipid levels, adjusting for sex, age and waist circumference. In addition Bonferroni correction was performed to account for multiple testing. Several variants of CETP , LCAT , PCSK9 , and PON1 (MAF > 0.05) were associated with HDL-C, LDL-C and TC levels at p < 0.05. The lead variants for association with HDL-C were rs17231520 in CETP (β = 0.139, p < 0.0001) and rs1109166 in LCAT (β = −0.044, p = 0.028). Lower LDL-C levels were associated with an intronic variant in PCSK9 (rs11806638 [β = −0.055, p = 0.027]) and increased TC was associated with a variant in PON1 (rs854558 [β = 0.040, p = 0.020]). In silico functional analyses indicated that these variants likely influence gene function through their effect on gene transcription. We replicated a strong association between CETP variants and HDL-C and between PCSK9 variant and LDL-C in West Africans, with two potentially functional variants and identified three novel variants in linkage disequilibrium in PON1 which were associated with increasing TC levels in Ghanaians. [ABSTRACT FROM AUTHOR]

Dyslipidaemia is a primary risk factor for cardiometabolic disease, causing over 17 million deaths globally in 2015. However, the burden of dyslipidaemia and factors associated with lipid levels remain unknown in many rural African populations. Therefore, this study evaluated the association of socio-demographic, anthropometric and behavioural factors with lipid levels in rural Ghana. The prevalence of hypercholesterolaemia, hypertriglyceridaemia and elevated LDL-C in the total population of 1839 (846 men and 993 women) was 4.02%, 2.12%, and 5.55% respectively and did not differ between genders. The prevalence of low HDL-C levels was 60.30% and differed (p = 0.005) between men (56.86%) and women (63.24%). Subcutaneous abdominal fat was associated with TC (β = 0.067, p = 0.015) and TG (β = 0.137, p<0.001) among women and LDL-C (β = 0.139, p = 0.006) and TC (β = 0.071, p = 0.048) among men. Body mass index was associated with TC (β = 0.010, p = 0.043) among men while waist circumference was associated with LDL-C (β = 0.116, p<0.001) and TG (β = 0.094, p<0.001) among women. Hip circumference was negatively associated (β = -0.053, p = 0.043) while visceral fat was positively associated with TG (β = 0.033, p = 0.022) among women. Socioeconomic status, education, being unmarried and employment were associated with HDL-C (β = 0.081, p = 0.004), LDL-C (β = 0.095, p = 0.004) and TG (β = 0.095, p = 0.001) all among women, and TC (β = 0.070, p = 0.010) among men, respectively. Nankana women had lower TC (β = -0.069, p = 0.001), and men lower TG levels (β = -0.084, p = 0.008) than the other ethnic groups. Tobacco smoking (β = 0.066, p = 0.024) and alcohol intake (β = 0.084, p = 0.001) were associated with HDL-C levels among men and women respectively. Further studies are required to investigate whether high prevalence of low HDL-C levels in this population presents with any adverse cardiovascular disease outcomes. Associations of education, employment and adiposity with lipid levels suggest that future societal advances and increases in the prevalence of obesity may lead to associated adverse health consequences. Monitoring and interventions are required to limit these effects. [ABSTRACT FROM AUTHOR]