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.

Morbidity and mortality profile of patients seen in medical emergency unit of a teaching hospital in Nigeria: A 4-year audit

Background: Ahmadu Bello University Teaching Hospital (ABUTH) Zaria is strategically located to serve as referral center for most stable and emergency cases in the northwestern part of Nigeria. Patients also come on self­referral. Objective: This study aimed to describe the pattern of medical presentation and outcomes at the emergency unit of ABUTH over a 4­year period. Materials and Methods: A review of medical admissions into the Emergency unit of ABUTH, Zaria, between January 2013 and December 2016 was carried out using the case records of patients as well as register of admissions and discharges, information obtained were entered into a predetermined questionnaire. Results: The patients admitted during the period numbered 5193, with age rangeof 15­92 years. There were 2895 (56.0%) males and 2298 (44.0%), with a male­to­female ratio of 1.3:1. Emergencies attributable to infectious diseases occurred with the highest frequency (20.6%), followed by gastrointestinal (20.5%), renal (14.5%), endocrine (13.8%),respiratory (12.4%),cardiac (9%), neurological (2.8%), and hematological (1.1%). There was a significantly (P < 0.001) higher occurrence of noncommunicable diseases (71.5%) than communicable diseases (28.5%), as well as higher male cases in renal, respiratory,hematological emergencies (P < 0.05). There were more admissions in the wet season, (April to September) while the October to January period consistently recorded the low admission rates. An increasing trend in emergency medical admissions was observed, being highest in the year 2016. The median duration of stay was 4.5 days (range of 0­12 days). The outcomes of admission revealed 470 (9%) deaths, 2012 (37%) direct discharges, and 2801 (54%) transfers to male or female medical wards. Cases of tetanus had the highest case fatality rate (45%) while hypertensive emergencies had the lowest (4%). Conclusion: There is a rising trend ofcommunicable as opposed to non-communicable diseases' emergencies in Zaria. Of the non-communicable diseases, incidence of gastro-intestinal emergencies was the highest while that of haematology was the least. The intra-hospital mortality rate attributable to medical emergencies is relatively lower in Zaria

Dysphagia following acute stroke and its effect on short-term outcome.

BACKGROUND: Dysphagia is assciated with numerous medical conditions including stroke, and there are wide variations in reported frequency of dysphagia in stroke survivors in the literature. Dysphagia has been shown to be an important risk factor for aspiration pneumonia and has profound impact on survivors. AIMS: This study aims to determine the frequency of dysphagia in stroke survivors and its effects on short-term outcome. METHODS: Consecutive patients hospitalised for first-ever acute stroke at Ahmadu Bello University Teaching Hospital Zaria, Nigeria, were prospectively enrolled from April 2015 to January 2017. Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS). Water swallowing test was used to screen patients for the presence of dysphagia. This was followed by swallowing provocative test which was aimed at evaluating swallowing reflexes. All the patients were then followed up till day 30. Outcome measures applied were 30-day mortality and functional impairment on the Modified Rankin Scale. RESULTS: Ninety-four patients (53 males and 41 females) with acute stroke were studied. Mean age of patients was 55.51 ± 15.7 years and 32 (34.4%) patients had dysphagia at presentation. Mean NIHSS score of patients with dysphagia was significantly higher than those without dysphagia. Aspiration pneumonia occurred more significantly in those with dysphagia. In multivariate logistic regression, only aspiration pneumonia was independently associated with 30-day mortality. CONCLUSION: The prevalence of dysphagia in this cohort of stroke patients was 34.4%, and the major independent determinant of 30-day mortality was development of aspiration pneumonia.

Metabolic syndrome in urban city of North-Western Nigeria: prevalence and determinants.

INTRODUCTION: The aim of this study was to investigate the prevalence of metabolic syndrome in Sokoto metropolis of North-Western Nigeria. METHODS: A cross-sectional community based study was carried out. Four hundred and ten subjects (201 males and 209 females) were recruited for the study using a multi-stage sampling technique. Demographic and the life style data was obtained from the participants. Evaluation of anthropometric variables, fasting blood sugar, lipid profiles, insulin resistance and blood pressure was performed. The classification of metabolic syndrome was based on the NCEP ATP III guidelines. RESULTS: The mean (SD) age of the sample population was 39.6 (14.4) years. The mean (SD) age of the male subjects was 38.4(14.9) years and that of the females was 40.8(13.9) years (p> 0.05). The overall prevalence of metabolic syndrome was 35.1% with the females having 42.83% and the males 27.36%. The frequencies of metabolic syndrome parameters in the study subjects were low HDL (56.1%), hypertension (46.1%), dysglycemia (32.7%), central obesity (28%), and elevated triglycerides (22.4%). Most of the women had low HDL (62.2%) and central obesity elevated (49.8%). CONCLUSION: Metabolic syndrome is common in residents of North-Western Nigeria, commoner in the females than males. Risk factors for metabolic syndrome should be detected in normal individuals for implementing effective preventive measures.