Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study.

BACKGROUND: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations. METHODS: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. FINDINGS: We included 197 918 individuals (1488 cases and 196 430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397 × 10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset ß=-2·00 [SE=0·57], p=0·0005, for African ancestry; and ß=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. INTERPRETATION: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease. FUNDING: The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research.

Assessment of sleep knowledge among medical and dental students in a Nigerian tertiary institution: a cross-sectional study.

PURPOSE: Sleep medicine is a rapidly growing field of Medicine globally. However, studies are lacking on the knowledge of Nigerian medical and dental students on sleep and the different types of sleep disorders. Thus, we assessed the knowledge, interest and awareness of Nigerian medical and dental students about sleep medicine. We also determined the factors associated with sleep knowledge among the medical and dental students. METHODS: We conducted this cross-sectional study from June to September 2021, among medical students at the Obafemi Awolowo University, Ile-Ife, Nigeria. The students' knowledge of sleep was assessed with the Assessment of Sleep Knowledge in Medical Education (ASKME) survey. The participants were classified as having low or high scores based on the proportion who gave a correct answer to 60% of the questions. RESULTS: Among the 488 students who completed the questionnaire, there was a male preponderance (55%). About three-quarters of the respondents (376, 77%) had a low sleep knowledge score. Age, year of study, and awareness about sleep medicine were the predictors of sleep knowledge. CONCLUSION: A significant proportion of the medical students had poor sleep knowledge scores. There is a need to incorporate teaching sleep medicine in the curriculum of medical students early in their training.

Knowledge, attitudes and practices related to stroke in Ghana and Nigeria: A SIREN call to action.

INTRODUCTION: Stroke is a prominent cause of death, disability, and dementia in sub-Saharan Africa (SSA). The Stroke Investigative Research and Education Network works collaboratively with stroke survivors and individuals serving as community controls to comprehensively characterize the genomic, sociocultural, economic and behavioral risk factors for stroke in SSA. PURPOSE: In this paper, we aim to: i) explore the attitudes, beliefs, and practices related to stroke in Ghana and Nigeria using the process of qualitative description; and ii) propose actions for future research and community-based participation and education. METHODS: Stroke survivors, their caregivers, health care professionals, and community representatives and faith-based leaders participated in one of twenty-six focus groups, which qualitatively explored community beliefs, attitudes and practices related to stroke in Ghana and Nigeria. Arthur Kleinman's Explanatory Model of Illness and the Social Ecological Model guided the questions and/or thematic analysis of the qualitative data. We hereby describe our focus group methods and analyses of qualitative data, as well as the findings and suggestions for improving stroke outcomes. RESULTS AND DISCUSSION: The major findings illustrate the fears, causes, chief problems, treatment, and recommendations related to stroke through the views of the participants, as well as recommendations for working effectively with the SIREN communities. Findings are compared to SIREN quantitative data and other qualitative studies in Africa. As far as we are aware, this is the first paper to qualitatively explore and contrast community beliefs, attitudes, and practices among stroke survivors and their caregivers, community and faith-based leaders, and health professionals in multiple communities within Nigeria and Ghana.

Association of traditional cardiovascular risk factors with carotid atherosclerosis among adults at a teaching hospital in south-western Nigeria.

BACKGROUND: Traditional cardiovascular risk factors (CVRFs), which include age, gender, hypertension, diabetes mellitus, dyslipidaemia, smoking, alcohol consumption, chronic kidney disease and obesity, have been shown to be associated with atherosclerosis. We aimed to evaluate the impact of traditional CVRFs on carotid atherosclerosis (CA) in a sample of Nigerian adults. METHODS: We examined 162 subjects with traditional CVRFs in a cross-sectional study. Demographic and clinical data, including history of hypertension, diabetes mellitus, smoking, alcohol intake and chronic kidney disease, as well as systolic and diastolic blood pressure, weight and height were collected. Serum creatinine, fasting blood glucose and lipid profiles were also determined. Carotid intima-media thickness (CIMT) and presence of carotid plaque (CP) were evaluated by high-frequency B-mode ultrasound. Chi-squared and regression analyses were carried out to determine associations between variables of CIMT and CVRF. RESULTS: Increased CIMT was associated with all CVRFs (p < 0.05) except gender (p > 0.05), while CP was associated with older age, obesity, hypertension and dyslipidaemia (p < 0.05). We found prevalence of increased CIMT was 53.7%, while that of CP was 16.1%. The prevalence of CA (increased CIMT and CP) also increased with increasing number of CVRFs in the subjects. Age ≥ 50 years, hypertension, dyslipidaemia, obesity and alcohol intake explained 78.7% of variance in CIMT, while age ≥ 50 years and hypertension explained 38.0% of variance in CP. CONCLUSIONS: CA was associated with presence and increasing number of traditional CVRFs. A significant percentage of variance in CA was, however, unexplained by traditional CVRFs.

Sonographic Evaluation of Endothelial Function in Brachial Arteries of Adult Stroke Patients.

OBJECTIVES: Brachial artery flow-mediated dilatation on sonography is used to evaluate endothelial dysfunction, which is a key event in the development of atherosclerosis and predates structural atherosclerotic lesions by many years. Atherosclerosis has been implicated in the pathophysiologic mechanisms of ischemic stroke. The aim of this study was to determine the association between brachial flow-mediated dilatation, the presence of cardiovascular risk factors, and acute stroke. METHODS: We evaluated right brachial arteries of 150 participants (50 stroke patients, 50 patients with cardiovascular risk factors, and 50 healthy control individuals) with B-mode sonography before and 5 minutes after sphygmomanometer cuff application to their forearms. Analysis of variance for multiple comparisons was used between each group. RESULTS: Mean ages of the stroke, risk factor, and control groups ± SD were 57.5 ± 14.8, 52.4 ± 16.0, and 56.1 ± 14.9 years, respectively (P = .235). Flow-mediated dilatation rates were 4.37% ± 1.50%, 5.62% ± 1.23%, and 10.33% ± 1.96% in the stroke, risk factor, and control groups (P ≤ .001). Dilatation was 3.79% ± 0.92% in ischemic stroke compared with 6.02% ± 1.62% in intracerebral hemorrhage (P < .001), but there was no significant difference in dilatation between ischemic stroke subtypes according to the Trial of ORG 10172 in Acute Stroke Treatment classification (P = .301). CONCLUSIONS: Brachial flow-mediated dilatation was significantly lower in patients with acute stroke compared with controls matched for vascular risk factors and healthy controls. Decreased vascular endothelial function in stroke patients was particularly related to cerebral infarction compared with intracerebral hemorrhage. Brachial flow-mediated dilatation did not differentiate ischemic stroke subtypes by the Trial of ORG 10172 in Acute Stroke Treatment classification. Flow-mediated dilatation was therefore found to be a marker of cardiovascular risk and a probable reactant in the acute phase of stroke.

Dyslipidaemia as a risk factor in the occurrence of stroke in Nigeria: prevalence and patterns.

INTRODUCTION: Stroke is a major public health problem worldwide. Hypertension, diabetes mellitus, dyslipidaemia and smoking are some of the common modifiable risk factors in the occurrence of stroke. Therefore, this study was designed to assess the prevalence and patterns of dyslipidaemia among individuals with acute stroke. METHODS: This is a retrospective descriptive cross-sectional study, carried out in the Departments of Medicine at the LAUTECH Teaching hospital, Ogbomoso and General Hospital, Orile-Agege, Lagos, South-West, Nigeria, over a 18-month period between September 2012 and February 2014. One hundred and six (106) patients with acute stroke confirmed with computed tomography (CT) brain scan were recruited. Clinical features, risk factors, lipid profiles and stroke patterns were identified. RESULTS: Mean age was significantly higher in ischaemic stroke compared to haemorrhagic (64.08±10.87 Vs, 56.21±12.38years, p=0.001). There was slight male preponderance in both stroke types (1.3:1). Out of 106 patients, 65 (61.3%) had ischaemic stroke, 38 (35.8%) intracerebral haemorrhage and 3 (2.9%) with subarachnoid haemorrhage. Dyslipidaemia is the most frequent risk factor (85.9%), followed by hypertension (66.0%) and diabetes mellitus (15.1%). Dyslipidaemia was significantly higher in the ischaemic stroke compared to haemorrhagic. Reduced HDL-cholesterol is the most prevalent fraction of lipid abnormalities (74.5%). CONCLUSION: Dyslipidaemia, particularly low HDL-C, was the most frequent risk factor in our patients with stroke. Hence, prevention of dyslipidaemia as well as other risk factors is key to reducing the burden of stroke in our country.