Gershim Asiki

A General Approach for Haplotype Phasing across the Full Spectrum of Relatedness

Many existing cohorts contain a range of relatedness between genotyped individuals, either by design or by chance. Haplotype estimation in such cohorts is a central step in many downstream analyses. Using genotypes from six cohorts from isolated populations and two cohorts from non-isolated populations, we have investigated the performance of different phasing methods designed for nominally ‘unrelated’ individuals. We find that SHAPEIT2 produces much lower switch error rates in all cohorts compared to other methods, including those designed specifically for isolated populations. In particular, when large amounts of IBD sharing is present, SHAPEIT2 infers close to perfect haplotypes. Based on these results we have developed a general strategy for phasing cohorts with any level of implicit or explicit relatedness between individuals. First SHAPEIT2 is run ignoring all explicit family information. We then apply a novel HMM method (duoHMM) to combine the SHAPEIT2 haplotypes with any family information to infer the inheritance pattern of each meiosis at all sites across each chromosome. This allows the correction of switch errors, detection of recombination events and genotyping errors. We show that the method detects numbers of recombination events that align very well with expectations based on genetic maps, and that it infers far fewer spurious recombination events than Merlin. The method can also detect genotyping errors and infer recombination events in otherwise uninformative families, such as trios and duos. The detected recombination events can be used in association scans for recombination phenotypes. The method provides a simple and unified approach to haplotype estimation, that will be of interest to researchers in the fields of human, animal and plant genetics.

The African Genome Variation Project shapes medical genetics in Africa

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis

Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda.

Objectives Recent publications suggest that fishing populations may be highly affected by the HIV epidemic. However, accurate data are scarce. The authors determined HIV and syphilis prevalence and associated risk factors in a fishing population of Lake Victoria in Uganda. Methods 10 188 volunteers aged ≥13 years from a census carried out in five fishing communities between February and August 2009 were invited to attend central study clinics established in each community. After informed consent, 2005 randomly selected volunteers responded to socio-demographic and risk assessment questions, provided blood for HIV testing and 1618 volunteers were also tested for syphilis. Risk factors were analysed using logistic regression. Results HIV and active syphilis (rapid plasma reagin titre ≥1:8) prevalences were 28.8% (95% CI 26.8 to 30.8) and 4.3% (95% CI 3.3 to 5.4), respectively, and high risk sexual behaviour was frequently reported. HIV prevalence was independently associated with female sex, increasing age, occupation (highest in fishermen), relationship to household head, self-reported genital sores and knowledge of an HIV infected partner. Alcohol consumption, syphilis and sexually transmitted infections (STIs) reported by health workers were associated with HIV in women, and genital discharge and inconsistent condom use in men. Syphilis prevalence was independently associated with age and alcohol consumption in women, and recent genital sores and sex under the influence of drugs in men. Conclusion This fishing population characterised by a very high HIV prevalence, high syphilis prevalence and frequently reported sexual risk behaviours, urgently needs improved STI services and targeted behavioural interventions.

High HIV incidence and socio-behavioral risk patterns in fishing communities on the shores of Lake Victoria, Uganda.

Background: We report on HIV acquisition and its associated risk factors in 5 fishing communities on the shores of Lake Victoria in Uganda. A cohort of 1000 HIV-uninfected at-risk volunteers aged 13 to 49 years were recruited in 2009 and followed up for 18 months. Methods: At enrollment and semiannual visits, socio-demographic and risk behavior data were collected through a structured questionnaire and blood samples tested for HIV and syphilis. Detailed life histories were collected from 78 volunteers using in-depth interviews. Results: Of the 1000 volunteers enrolled, 919 (91.9%) were followed up, with 762 (76.2%) reaching the study end points (either seroconverted or completed 4 visits). There were 59 incident cases in 1205.6 person-years at risk (PYAR), resulting in an incidence rate of 4.9 (95% CI = 3.8 to 6.3) per 100 PYAR. The highest HIV incidence rates were among those working in bars (9.8/100 PYAR [4.7–20.6]), protestants (8.6/100 PYAR [5.8–12.7]), those aged 13 to 24 years (7.5/100 PYAR [5.2–11.0]), and new immigrants (6.6/100 PYAR [4.9–8.9]). HIV infection was independently associated with being young (adjusted hazard ratio (aHR) = 2.5 [95% CI = 1.3–4.9]), reporting genital sores/discharge recently (aHR = 2.8 [1.6–5.0]), regular alcohol consumption (aHR = 3.3 [1.6–6.1]), use of marijuana (aHR = 2.9 [1.0–8.0]), cigarette smoking (aHR = 3.6 [1.4–9.3]), and religion (compared with Catholics, Protestants had aHR = 2.7 [1.4–5.3] and Muslims had aHR = 2.3 [1.1–4.8]). Conclusions: These fishing communities experienced high HIV infection, which was mainly explained by high-risk behavior. There is an urgent need to target HIV prevention and research efforts to this vulnerable and neglected group.

The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies

The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to mrc@mrcuganda.org or the corresponding author.

Pneumonic Plague Cluster, Uganda, 2004

In a case cluster, pneumonic plague transmission was compatible with respiratory droplet rather than aerosol transmission.

Sociodemographic distribution of non-communicable disease risk factors in rural Uganda: a cross-sectional study

BACKGROUND Non-communicable diseases (NCDs) are rapidly becoming leading causes of morbidity and mortality in low- and middle-income countries, including those in sub-Saharan Africa. In contrast to high-income countries, the sociodemographic distribution, including socioeconomic inequalities, of NCDs and their risk factors is unclear in sub-Saharan Africa, particularly among rural populations. METHODS We undertook a cross-sectional population-based survey of 7809 residents aged 13 years or older in the General Population Cohort in south-western rural Uganda. Information on behavioural, physiological and biochemical risk factors was obtained using standardized methods as recommended by the WHO STEPwise Approach to Surveillance. Socioeconomic status (SES) was determined by principal component analysis including household features, ownership, and occupation and education of the head of household. RESULTS SES was found to be associated with NCD risk factors in this rural population. Smoking, alcohol consumption (men only) and low high-density lipoprotein (HDL) cholesterol were more common among those of lower SES. For example, the prevalence of smoking decreased 4-fold from the lowest to the highest SES groups, from 22.0% to 5.7% for men and 2.2% to 0.4% for women, respectively. In contrast, overweight, raised blood pressure, raised HbA1c (women only) and raised cholesterol were more common among those of higher SES. For example, the prevalence of overweight increased 5-fold from 2.1% to 10.1% for men, and 2-fold from 12.0% to 23.4% for women, from the lowest to highest SES groups respectively. However, neither low physical activity nor fruit, vegetable or staples consumption was associated with SES. Furthermore, associations between NCD risk factors and SES were modified by age and sex. CONCLUSIONS Within this rural population, NCD risk factors are common and vary both inversely and positively across the SES gradient. A better understanding of the determinants of the sociodemographic distribution of NCDs and their risk factors in rural sub-Saharan African populations will help identify populations at most risk of developing NCDs and help plan interventions to reduce their burden.

Data Resource Profile: Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network)

Data Resource Profile : Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network)

A pilot study to evaluate aflatoxin exposure in a rural Ugandan population

The fungal metabolite aflatoxin is a common contaminant of foodstuffs, especially when stored in damp conditions. In humans, high levels can result in acute hepatic necrosis and death, while chronic exposure is carcinogenic. We conducted a pilot study nested within an existing population cohort (the General Population Cohort), to assess exposure to aflatoxin, among people living in rural south‐western Uganda.