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.

Stigmatizing attitude towards mental illness, disabilities, emotional and behavioural disorders, among healthcare students in a Tropical University College of Health Sciences.

BACKGROUND: Stigma toward mental illness (MI), physical disability (DA), and emotional/behavioral disorders (EBD) has been identified as a form of violence and a cause of nontake-up of help by people in need. Stigmatization can aggravate an individual's feeling of rejection and incompetence and can be detrimental to treatment-seeking and adherence behaviors. This study evaluated the attitude of healthcare students toward MI, DA, and EBDs. MATERIALS AND METHODS: This study employed a cross-sectional survey method. A disproportionate stratified sampling technique was used to recruit participants. Sixty five consenting students who met the inclusion criteria were consecutively recruited from each clinical department of the college. The students were selected from the five clinical departments of the College (Nursing sciences, Medical Rehabilitation, Radiography, Medical laboratory science, and Medicine). The questionnaires on stigmatizing attitudes toward MI, EBD, and DA were self-administered. Descriptive statistics of frequency count, percentage, range, mean, and standard deviation were used to summarize participants' sociodemographic data and their questionnaire scores. Inferential statistics of Spearman rank order correlation was used to test for correlation; Mann-Whitney U test was used to test the influence of gender, religion, and family history; and Kruskal-Wallis test was used to test the influence of department of study and level of study. Alpha level was set at 0.05. RESULTS: Three hundred twenty seven students comprising 164 (50.2%) males and 163 (49.8%) females participated. Mean age of participants was 22.89 ± 2.05 years. 45.3% of the participants reported positive family history of one or a combination of MI, DA, and EBDs. The study observed poor attitude toward MI and fair attitude toward DA and EBD. There were significant correlations between attitudes toward MI and disability (r = 0.36, P =.000033), MI and EBD (r = 0.23, P =.000023), disability and EBD (r = 0.46, P =.000001), and age and attitude toward disability (r = 0.15, P =.009). Females had significantly more positive attitude toward disability (P =.03) and EBDs (P =.03). Nursing students also demonstrated the most positive attitudes toward MI (P =.03) and EBD (P =.000416), while final year students demonstrated the most positive attitudes toward MI (P =.00145) and EBDs (P =.03). CONCLUSIONS: There was a poor attitude toward MI and a fair attitude toward DA and EBD. Attitude toward MI, DA, and EBD correlated significantly with one another. Older students, females, and higher levels of training in the healthcare profession were associated with more positive attitudes toward MI, DA, and EBDs.

Epidemiology of Acute Symptomatic Seizures among Adult Medical Admissions.

Acute symptomatic seizures are seizures occurring in close temporal relationship with an acute central nervous system (CNS) insult. The objective of the study was to determine the frequency of presentation and etiological risk factors of acute symptomatic seizures among adult medical admissions. It was a two-year retrospective study of the medical files of adults patients admitted with acute symptomatic seizures as the first presenting event. There were 94 cases of acute symptomatic seizures accounting for 5.2% (95% CI: 4.17-6.23) of the 1,802 medical admissions during the period under review. There were 49 (52.1%) males and 45 (47.9%) females aged between 18 years and 84 years. The etiological risk factors of acute symptomatic seizures were infections in 36.2% (n = 34) of cases, stroke in 29.8% (n = 28), metabolic in 12.8% (n = 12), toxic in 10.6% (n = 10), and other causes in 10.6% (n = 10). Infective causes were more among those below fifty years while stroke was more in those aged fifty years and above. CNS infections and stroke were the prominent causes of acute symptomatic seizures. This is an evidence of the "double tragedy" facing developing countries, the unresolved threat of infectious diseases on one hand and the increasing impact of noncommunicable diseases on the other one.