KCNS1 and GCH1 were investigated for their association with pain intensity in black Southern Africans with HIV-associated sensory neuropathy. Previously associated single nucleotide polymorphisms (SNPs) were supplemented with population-specific tagSNPs. No SNPs in KCNS1 were individually associated with pain intensity. However, several haplotypes of population-specific tagSNPs correlated with pain intensity on univariate analysis and after correcting for age, gender, and CD4 T-cell count. This suggests that the haplotypes incorporate the causative SNP(s). No SNPs or haplotypes in GCH1 were associated with pain intensity. The study shows the importance of conducting association analyses in different ethnic groups, using population-based marker selection.

ObjectiveThe latest genome-wide association studies of obesity-related traits have identified several genetic loci contributing to body composition (BC). These findings have not been robustly replicated in African populations, therefore, this study aimed to assess whether European BC-associated gene loci played a similar role in a South African black population.MethodsA replication and fine-mapping study was performed in participants from the Birth to Twenty cohort (N = 1,926) using the Metabochip. Measurements included body mass index (BMI), waist and hip circumference, waist-to-hip ratio (WHR), total fat mass, total lean mass and percentage fat mass (PFM).ResultsSNPs in several gene loci, including SEC16B (Padj <  9.48 × 10−7), NEGR1 (Padj < 1.64 × 10−6), FTO (Padj < 2.91 × 10−5), TMEM18 (Padj < 2.27 × 10−5), and WARS2 (Padj < 3.25 × 10−5) were similarly associated (albeit not at array-wide signficance (P ≤ 6.7 × 10−7) with various phenotypes including fat mass, PFM, WHR linked to BC in this African cohort, however the associations were driven by different sentinel SNPs. More importantly, DXA-derived BC measures revealed stronger genetic associations than simple anthropometric measures. Association signals generated in this study were shared by European and African populations, as well as unique to this African cohort. Moreover, sophisticated estimates like DXA measures enabled an enhanced characterisation of genetic associations for BC traits.ConclusionResults from this study suggest that in-depth genomic studies in larger African cohorts may reveal novel SNPs for body composition and adiposity, which will provide greater insight into the aetiology of obesity.

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We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.

BackgroundCardiovascular diseases (CVDs) are the leading cause of non-communicable disease deaths globally, with hypertension being a major risk factor contributing to CVDs. Blood pressure is a heritable trait, with relatively few genetic studies having been performed in Africans. This study aimed to identify genetic variants associated with variance in systolic (SBP) and diastolic (DBP) blood pressure in black South Africans.MethodsGenotyping was performed using the Metabochip in a subset of participants (mixed sex; median age 17.9) and their adult female caregivers (median age 41.0) from the Birth to Twenty cohort (n = 1947). Data were analysed as a merged dataset (all participants and caregivers together) in GEMMA (v0.94.1) using univariate linear mixed models, incorporating a centered relatedness matrix to account for the relatedness between individuals and with adjustments for age, sex, BMI and principal components of the genotype information.ResultsAssociation analysis identified regions of interest in the NOS1AP (DBP: rs112468105 - p = 7.18 × 10−5 and SBP: rs4657181 - p = 4.04 × 10−5), MYRF (SBP: rs11230796 - p = 2.16 × 10−7, rs400075 - p = 2.88 × 10−7) and POC1B (SBP: rs770373 - p = 7.05 × 10−5, rs770374 - p = 9.05 × 10−5) genes and some intergenic regions (DACH1|LOC440145 (DBP: rs17240498 - p = 4.91 × 10−6 and SBP: rs17240498 - p = 2.10 × 10−5) and INTS10|LPL (SBP: rs55830938 - p = 1.30 × 10−5, rs73599609 - p = 5.78 × 10−5, rs73667448 - p = 6.86 × 10−5)).ConclusionsThe study provided further insight into the contribution of genetic variants to blood pressure in black South Africans. Future functional and replication studies in larger samples are required to confirm the role of the identified loci in blood pressure regulation and whether or not these variants are African-specific.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0321-6) contains supplementary material, which is available to authorized users.

The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so.PLOS Computational Biology | https://doi.org/10.1371/journal.pcbi

BackgroundNinety-seven independent single nucleotide polymorphisms (SNPs) are robustly associated with adult body mass index (BMI kg/m2) in Caucasian populations. The relevance of such variants in African populations at different stages of the life course (such as childhood) is unclear. We tested whether a genetic risk score composed of the aforementioned SNPs was associated with BMI from infancy to early adulthood. We further tested whether this genetic effect was mediated by conditional weight gain at different growth periods. We used data from the Birth to Twenty Plus Cohort (Bt20+), for 971 urban South African black children from birth to 18 years. DNA was collected at 13 years old and was genotyped using the Metabochip (Illumina) array. The weighted genetic risk score (wGRS) for BMI was constructed based on 71 of the 97 previously reported SNPs.ResultsThe cross-sectional association between the wGRS and BMI strengthened with age from 5 to 18 years. The significant associations were observed from 11 to 18 years, and peak effect sizes were observed at 13 and 14 years of age. Results from the linear mixed effects models showed significant interactions between the wGRS and age on longitudinal BMI but no such interactions were observed in sex and the wGRS. A higher wGRS was associated with an increased relative risk of belonging to the early onset obese longitudinal BMI trajectory (relative risk = 1.88; 95%CI 1.28 to 2.76) compared to belonging to a normal longitudinal BMI trajectory. Adolescent conditional relative weight gain had a suggestive mediation effect of 56% on the association between wGRS and obesity risk at 18 years.ConclusionsThe results suggest that genetic susceptibility to higher adult BMI can be tracked from childhood in this African population. This supports the notion that prevention of adult obesity should begin early in life. The genetic risk score combined with other non-genetic risk factors, such as BMI trajectory membership in our case, has the potential to be used to screen for early identification of individuals at increased risk of obesity and other related NCD risk factors in order to reduce the adverse health risk outcomes later.Electronic supplementary materialThe online version of this article (10.1186/s12263-018-0613-7) contains supplementary material, which is available to authorized users.

Aim To evaluate the association between loss-of-function (LOF) PCSK9 variants (A433T/rs28362263 and C679X/rs28362286) and biomarkers of cardiometabolic risk, specifically fasting glucose and low density lipoprotein cholesterol (LDL-C) concentrations. Methods Our study comprised 757 male and female black South African adolescents (mean age 18.0 ± 0.5 years) who are part of the Birth to Twenty Plus Cohort and had been genotyped for the two above-mentioned variants. Anthropometric measures were completed and fasting plasma glucose and lipid analysis were performed using standard procedures. Results The median and interquartile range of fasting glucose and LDL-C for the whole group were 4.60 (4.36–4.88) mmol/L and 1.67 (1.25–2.14) mmol/L, respectively. After adjusting for sex, association between the biomarkers and A443T was not significant. However, C679X carriers displayed 0.30 [95% CI (−0.57, −0.02); p = 0.035] mmol/L lower fasting glucose and 0.50 [95% CI (−0.74, −0.26); p < 0.001) mmol/L lower LDL-C concentrations compared to non-carriers. Conclusions Our results indicate for the first that the C679X variants associated with low fasting glucose levels during adolescents as had been known for LDL-C. In view that a similar finding was reported in older black South African adults, therefore, the correlation of lower fasting glucose and LDL-C levels with C679X is observed from an early age to adulthood.