Multi-Trait Polygenic Scores for COPD and COPD Exacerbations Implicate Druggable Proteins.

Objectives: To construct multi-trait polygenic scores (PRS) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validate their performance in diverse cohorts, and identify PRS-related proteins for potential therapeutic targeting.

Design: Prospective cohort studies.

Setting: Genetic Epidemiology of COPD (COPDGene; 2007-present), Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE; 2005-2008), Mass General Brigham Biobank (MGBB; 2010-present), All of Us (2016-present), and UK Biobank (UKB; 2006-present).

Development and Validation of Polygenic Risk Scores for Blood Pressure Traits in Continental African Populations.

Background: Most polygenic risk scores (PRS) have been developed in European populations, frequently leading to limited transferability across diverse ancestry populations. This study aimed to develop and evaluate PRS for blood pressure (BP) traits in continental African populations and investigate how African genetic diversity influences PRS performance.

Methods: We generated PRS for systolic BP, diastolic BP, pulse pressure, and hypertension.

SHBG, testosterone and type 2 diabetes risk in middle-aged African women: exploring the impact of HIV and menopause.

Context: Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk.

Objective: To investigate whether the associations between SHBG, testosterone and T2D risk differ by HIV and menopausal status in Black African women living with (WH) and without HIV (WOH).

Design: Cross-sectional observational.

Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals.

Introduction: Observational studies have identified associations between hematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limitation and investigate the causal effect of hematological traits such as white blood cell (WBC), platelets (PLT), and red blood cell (RBC) on T2D in individuals of African ancestry.

Sex hormone-binding globulin, testosterone and type 2 diabetes risk in middle-aged African women: exploring the impact of HIV and menopause.

Objectives: Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk. We investigated whether these associations differ by HIV and menopausal status in Black South African women living with (WLWH) and without HIV (WLWOH).

Design: Cross-sectional observational.

SHBG, Free Testosterone, and Type 2 Diabetes Risk in Middle-aged African Men: A Longitudinal Study.

Objectives: To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism.

Design: This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.

Regional Adiposity and Insulin Sensitivity-Interactions With Menopause and HIV in Middle-Aged Black African Women.

Objective: To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women.

Methods: Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative women (n = 21); premenopausal women living with HIV (LWH; n = 11); postmenopausal HIV-negative women (n = 42); and postmenopausal women LWH (n = 18) underwent the following tests: body composition (dual-energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation, and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size, and mRNA expression of adipokines, inflammation, and estrogen receptors (ER).

Results: Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status.

Variability of polygenic prediction for body mass index in Africa.

Background: Polygenic prediction studies in continental Africans are scarce. Africa's genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required.

Correction: Udosen et al. Meta-Analysis and Multivariate GWAS Analyses in 80,950 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits. 2023, , 2164.

In the original publication [...

Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study.

Background: Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits.

Postprandial glucose variability and clusters of sex hormones, liver enzymes, and cardiometabolic factors in a South African cohort of African ancestry.

Introduction: This study aimed to, first, determine the clusters of sex hormones, liver enzymes, and cardiometabolic factors associated with postprandial glucose (PPG) and, second to evaluate the variation these clusters account for jointly and independently with polygenic risk scores (PRSs) in South Africans of African ancestry men and women.

Research Design And Methods: PPG was calculated as the integrated area under the curve for glucose during the oral glucose tolerance test (OGTT) using the trapezoidal rule in 794 participants from the Middle-aged Soweto Cohort. Principal component analysis was used to cluster sex hormones, liver enzymes, and cardiometabolic factors, stratified by sex.

Factors associated with frequency of fruit and vegetable consumption among selected sub-Saharan African populations: evidence from the Cardiovascular H3Africa Innovation Resource Project.

Background: Frequent fruit and vegetable consumption is considered a promising dietary behaviour that protects health. However, most existing studies about the factors associated with this phenomenon among Africans are based on single-country reports, apart from one meta-regression combining smaller studies. This study harmonized large datasets and assessed factors associated with the frequency of fruit and vegetable consumption in this population.

The association of menopause with cardiometabolic disease risk factors in low- and middle-income countries: a systematic review and meta-analyses.

Importance: Menopause is an integral part of women's health, and studies in high-income countries have shown an increase in cardiometabolic disease (CMD) risk factors in postmenopausal compared with premenopausal women. However, to date, no study has combined and assessed such studies across low- and middle-income countries. This would better inform early monitoring and intervention strategies for reducing CMD risk factor levels in midlife women in these regions.

Leveraging information between multiple population groups and traits improves fine-mapping resolution.

Statistical fine-mapping helps to pinpoint likely causal variants underlying genetic association signals. Its resolution can be improved by (i) leveraging information between traits; and (ii) exploiting differences in linkage disequilibrium structure between diverse population groups. Using association summary statistics, MGflashfm jointly fine-maps signals from multiple traits and population groups; MGfm uses an analogous framework to analyse each trait separately.

The case for precision medicine in the prevention, diagnosis, and treatment of cardiometabolic diseases in low-income and middle-income countries.

Cardiometabolic diseases are the leading preventable causes of death in most geographies. The causes, clinical presentations, and pathogenesis of cardiometabolic diseases vary greatly worldwide, as do the resources and strategies needed to prevent and treat them. Therefore, there is no single solution and health care should be optimised, if not to the individual (ie, personalised health care), then at least to population subgroups (ie, precision medicine).

The African Society of Human Genetics successfully launches global data science workshops.

To accelerate the impact of African genomics on human health, data science skills and awareness of Africa's rich genetic diversity must be strengthened globally. We describe the first African genomics data science workshop, implemented by the African Society of Human Genetics (AfSHG) and international partners, providing a framework for future workshops.

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.

Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry.

Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function.

Despite recent efforts to increase diversity in genome-wide association studies (GWASs), most loci currently associated with kidney function are still limited to European ancestry due to the underlying sample selection bias in available GWASs. We set out to identify susceptibility loci associated with estimated glomerular filtration rate (eGFRcrea) in 80027 individuals of African-ancestry from the UK Biobank (UKBB), Million Veteran Program (MVP), and Chronic Kidney Disease genetics (CKDGen) consortia.We identified 8 lead SNPs, 7 of which were previously associated with eGFR in other populations.

Genome-wide association analysis of cystatin-C kidney function in continental Africa.

Background: Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance.