Dataset Information

Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.

ABSTRACT: Cognitive function is an indicator for global physical and mental health, and cognitive impairment has been associated with poorer life outcomes and earlier mortality. A standard cognition test, adapted to a rural-dwelling African community, and the Oxford Cognition Screen-Plus were used to capture cognitive performance as five continuous traits (total cognition score, verbal episodic memory, executive function, language, and visuospatial ability) for 2,246 adults in this population of South Africans. A novel common variant, rs73485231, reached genome-wide significance for association with episodic memory using data for ~14 million markers imputed from the H3Africa genotyping array data. Window-based replication of previously implicated variants and regions of interest support the discovery of African-specific associated variants despite the small population size and low allele frequency. This African genome-wide association study identifies suggestive associations with general cognition and domain-specific cognitive pathways and lays the groundwork for further genomic studies on cognition in Africa.

SUBMITTER: Soo CC

PROVIDER: S-EPMC10043003 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.

Soo Cassandra C CC Brandenburg Jean-Tristan JT Nebel Almut A Tollman Stephen S Berkman Lisa L Ramsay Michèle M Choudhury Ananyo A

Communications biology 20230327 1

Cognitive function is an indicator for global physical and mental health, and cognitive impairment has been associated with poorer life outcomes and earlier mortality. A standard cognition test, adapted to a rural-dwelling African community, and the Oxford Cognition Screen-Plus were used to capture cognitive performance as five continuous traits (total cognition score, verbal episodic memory, executive function, language, and visuospatial ability) for 2,246 adults in this population of South Afr ...[more]

PMID: 36973338

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Project description:Globally, South Africa hosts the highest number of people living with HIV (PLHIV) and the unique legacy of internal labour migration continues to be a major driver of the regional epidemic, interrupting treatment-as-prevention efforts. The study examined levels, trends, and predictors of migration in rural KwaZulu-Natal Province, South Africa, using population-based surveillance data from 2005 through 2017. We followed 69 604 adult participants aged 15-49 years and recorded their migration events (i.e., out-migration from the surveillance area) in 423 038 person-years over 525 397 observations. Multiple failure Cox-regression models were used to measure the risk of migration by socio-demographic factors: age, sex, educational status, marital status, HIV, and community antiretroviral therapy (ART) coverage. Overall, 69% of the population cohort experienced at least one migration event during the follow-up period. The average incidence rate of migration was 9.96 events and 13.23 events per 100 person-years in women and men, respectively. Migration rates declined from 2005 to 2008 then peaked in 2012 for both women and men. Adjusting for other covariates, the risk of migration was 3.4-times higher among young women aged 20-24 years compared to those aged ≥ 40 years (adjusted Hazard Ratio [aHR] = 3.37, 95% Confidence Interval [CI]: 3:19-3.57), and 2.9-times higher among young men aged 20-24 years compared to those aged ≥ 40 years (aHR = 2.86, 95% CI:2.69-3.04). There was a 9% and 27% decrease in risk of migration among both women (aHR = 0.91, 95% CI: 0.83 - 0.99) and men (aHR = 0.73, 95% CI 0.66 - 0.82) respectively per every 1% increase in community ART coverage. Young unmarried women including those living with HIV, migrated at a magnitude similar to that of their male counterparts, and lowered as ART coverage increased over time, reflecting the role of improved HIV services across space in reducing out-migration. A deeper understanding of the characteristics of a migrating population provides critical information towards identifying and addressing gaps in the HIV prevention and care continuum in an era of high mobility.

Project description:BackgroundInfectious disease-related stigma is a pervasive global issue that impedes disease control efforts by increasing reluctance to seek treatment or engagement in prevention behaviors for fear of ostracism. Despite this, there is limited research on COVID-19 stigma in Africa, specifically rural South Africa, which has faced infectious disease-related stigma throughout the HIV epidemic.MethodsPopulation-based surveys were conducted among 1,662 adults living in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area in Mpumalanga, South Africa, in August-October 2020 and August-October 2021. Surveys measured anticipated COVID-19-related stigma from low to high levels. Changes in stigma between surveys were compared using Wilcoxon ranked sign tests, and log-binomial models estimated the association between socio-demographic factors and anticipated stigma at both intervals. Qualitative interviews were conducted in 2022 among 31 adults who completed the original surveys, and the data were analyzed thematically to describe anticipated, perceived, and enacted stigma.ResultsAnticipated stigma significantly decreased from the first to the second survey (p-value:<0.0001). Stigma was significantly higher among older age groups. In 2020, those less knowledgeable about COVID-19 were 2.24 times as likely to have higher levels of anticipated stigma compared to those who were more knowledgeable (RR:2.24, 95% CI: 1.90,2.64). Fear of being stigmatized influenced willingness to disclose infection. Participants perceived COVID-19 stigma as similar to HIV/AIDS stigma, but concern and fear reduced over time, with differences observed across generations and sexes. For some, fear of death and mistrust of others endorsed enacting stigma toward others.ConclusionWhile COVID-19 stigma decreased over time in rural South Africa, different forms of stigma persisted and influenced participants' willingness to reveal their COVID-19 infection status. Given South Africa's history with infectious disease-related stigma hindering public health efforts, it is crucial that government bodies prioritize strategies to mitigate stigma in rural communities.

Project description:Understanding spatial configuration of sexual network structure is critical for effective use of HIV preventative interventions in a community. However, this has never been described at the population level for any setting in sub-Saharan Africa. We constructed the comprehensive geospatial sexual network among new heterosexual partnerships in rural KwaZulu-Natal, South Africa. In the Africa Health Research Institute (AHRI)'s population-based surveillance, we identified stable sexual partnerships among individuals (≥15 years) from 2003 to 2016. Sexual partnerships and residency were recorded via household surveys (every 4-6 months). We geolocated residents and migration events and mapped the geospatial linkages of sexual partners at the start of sexual partnerships. In a grid composed by 108 cells (nodes; 3kmx3km per cell) covering the surveillance area (438km2), we calculated the degree of connectivity and centrality of the nodes and examined their association with HIV prevalence and incidence per cell. Of 2401 new sexual partnerships, 21% (n = 495) had both partners living within the surveillance area at the start of sexual partnerships, and 76% (376/495) were linked to the geographic HIV cluster with high HIV prevalence identified in a peri-urban community. Overall, 57 nodes had at least one connection to another node. The nodes in the peri-urban cluster had higher connectivity (mean = 19, range: 9-32), compared to outside the cluster (6, range: 1-16). The node's degree of connectivity was positively associated with HIV prevalence of the cell (Pearson correlation coefficient = 0.67; p <0.005). The peri-urban cluster contained nine of the 10 nodes that composed of a single large central module in the community. About 17% of sexual partnerships (n = 421) were formed between a resident and a non-resident partner who out-migrated. Most of these non-resident partners lived in KwaZulu-Natal (86.7%), followed by Gauteng (9.7%), and the median distance between a resident and a non-resident partner was 50.1km (IQR: 23.2-177.2). We found that the peri-urban HIV cluster served as the highly connected central node of the network for sexual partnership formation. The network was also connected beyond the surveillance area across South Africa. Understanding spatial sexual network can improve the provision of spatially targeted and effective interventions.

Project description:BackgroundAd hoc assumptions about the unobserved infection event, which is known only to occur between the latest-negative and earliest-positive test dates, can lead to biased HIV incidence rate estimates. Using a G-imputation approach, we infer the infection dates from covariate data to estimate the HIV incidence rate in a hyper-endemic South African setting.MethodsA large demographic surveillance system has annually tested a cohort of HIV-uninfected participants living in the KwaZulu-Natal province. Using this data, we estimated a cumulative baseline hazard function and the effects of time-dependent covariates on the interval censored infection dates. For each HIV-positive participant in the cohort, we derived a cumulative distribution function and sampled multiple infection dates conditional on the unique covariate values. We right censored the data at the imputed dates, calculated the annual HIV incidence rate per 100 person-years, and used Rubin's rules to obtain the 95% confidence intervals.ResultsA total of 20,011 uninfected individuals with a repeat HIV test participated in the incidence cohort between 2005 and 2018. We observed 2,603 infections per 58,769 person-years of follow-up among women and 845 infections per 41,178 person-years of follow-up among men. Conditional on age and circumcision status (men only), the female HIV incidence rate declined by 25%, from 5.0 to 3.7 infections per 100 person-years between 2014 and 2018. During this period, the HIV incidence rate among men declined from 2.1 to 1.1 infections per 100 person-years-a reduction of 49%. We observed similar reductions in male and female HIV incidence conditional on condom-use, marital status, urban residential status, migration history, and the HIV prevalence in the surrounding community.ConclusionWe have followed participants in one of the world's largest and longest running HIV cohorts to estimate long-term trends in the population-wide incidence of infection. Using a G-imputation approach, we present further evidence for HIV incidence rate declines in this hyper-endemic South African setting.

Dataset Information

Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.

Publications

Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.

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