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BACKGROUND: Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards the realization of the global application of precision medicine. The African and African admixed populations enable mapping of complex traits given their greater levels of genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. METHODS: Here we perform a comprehensive genome-wide assessment of Parkinson’s disease (PD) in 197,918 individuals (1,488 cases; 196,430 controls) of African and African admixed ancestry, characterizing population-specific risk, differential haplotype structure and admixture, coding and structural genetic variation and polygenic risk profiling. FINDINGS: We identified a novel common risk factor for PD and age at onset at the GBA1 locus (risk, rs3115534-G; OR=1.58, 95% CI = 1.37 – 1.80, P=2.397E-14; age at onset, BETA =−2.004, SE =0.57, P = 0.0005), that was found to be rare in non-African/African admixed populations. Downstream short- and long-read whole genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. However, we identified that this signal mediates PD risk via expression quantitative trait locus (eQTL) mechanisms. While previously identified GBA1 associated disease risk variants are coding mutations, here we suggest a novel functional mechanism consistent with a trend in decreasing glucocerebrosidase activity levels. Given the high population frequency of the underlying signal and the phenotypic characteristics of the homozygous carriers, we hypothesize that this variant may not cause Gaucher disease. Additionally, the prevalence of Gaucher’s disease in Africa is low. INTERPRETATION: The present study identifies a novel African-ancestry genetic risk factor in GBA1 as a major mechanistic basis of PD in the African and African admixed populations. This striking result contrasts to previous work in Northern European populations, both in terms of mechanism and attributable risk. This finding highlights the importance of understanding population-specific genetic risk in complex diseases, a particularly crucial point as the field moves toward precision medicine in PD clinical trials and while recognizing the need for equitable inclusion of ancestrally diverse groups in such trials. Given the distinctive genetics of these underrepresented populations, their inclusion represents a valuable step towards insights into novel genetic determinants underlying PD etiology. This opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk.

Background: The clinical course of Parkinson's disease (PD) is not limited to motor symptoms (tremor, bradykinesia, rigidity, gait problems and imbalance). A variety of non-motor symptoms (NMS) such as psychiatric, gastrointestinal, cognitive, sudomotor, autonomic, sleep and sensory disorders which occur commonly are usually underappreciated as features of PD. This is a short report which documents NMS in a group of PD patients in Port Harcourt.Method: Thirty -six patients with Parkinson's disease attending the neurology clinic of University of Port Harcourt Teaching Hospital were studied. The characteristics of the PD subjects and some non-motor symptoms were documented from direct interview as part of a larger study investigating Health related quality of life in PD.Results: Mean age was 64.3 ± 10.9 years (range 43- 86) and 27 were subjects were males and 9 were females. Persistent low mood was reported in30(83.3%), 27 (75%) had body pains and olfactory problems, 17 ( 47.2%) reported drooling of saliva and difficulty remembering events. 11 (30.6%) and 12 (33.3%) reported excessive daytime sleepiness and difficulty falling asleep respectively. Difficulty swallowing was reported in 7 (19.4%) and sweatingdisturbance in 10 (27.8%) patients.Conclusion: Non-motor symptoms occur in PD patients in Port Harcourt, Nigeria and awareness needs to be created among patients and health care providers on the presence and burden of NMS in PD patients in order to offer holistic care and improve quality of life in PD patients.Keywords: Non-motor symptoms; Parkinson's disease; Nigeria

Background The diagnosis of acute ischaemic stroke is sometimes straightforward. The sudden onset of a focal neurologic deficit in a recognizable vascular distribution with a common presentation - such as hemiparesis, facial weakness and aphasia - identifies a common syndrome of acute stroke. I But differential diagnostic problems remain because there are some non-vascular disorders which "mimic" stroke. Such mimics have clinical pictures that appear identical to stroke. I However, standard acute neuroimaging with non-contrast CT scanning will discover some of these mass lesions mimicking stroke. We therefore present a brief case report on cerebral toxoplasmosis as a stroke mimicMethods The case records of a patient who presented with cerebral toxoplasmosis mimicking a stroke and a review of the literature using google, Medline and PubMed search as well as available literature on the subject were utilized.Results We present a 52 year banker, a known hypertensive of2 years duration who claims good adherence to medications. He presented to us 16 days after he a history of inability to move the left side of his body and other neurologic features suggestive of a right hemispheric ischaemic stroke. Brain CT showed features of cerebral toxoplasmosis and he was found to be seropositive HIV 1. The patient was placed on pyrimethamine, sulphadiazine, dexamethasone, antihypertensives and HAART. He made remarkable improvement on discharge and follow up.Conclusion It is important for physicians to have a high index of suspicion for stroke mimics and ensure that radiologic brain imaging is done in all suspected stroke patients in order to ensure appropriate diagnosis and treatment as in this index case.

Background: With the advent of free treatment with highly active anti-retroviral therapy across Nigeria, people living with HIV I AIDS (PLWHA) now live longer. However, the burden of the disease still remains high. Aside from quantity of life lived, quality oflife(QOL) as a second key component of the burden of the disease has therefore come to the fore. There is increasing body of literature on quality of life among PLWHA from other parts of the country. However, there is still paucity of data in our environment. This study assessed the QOL of PLWHA attending the anti-retroviral clinic in the University of Port Harcourt Teaching Hospital, Port Harcourt, South - South region of Nigeria.Methods: A descriptive cross-sectional study design was used. Five hundred (500) PLWHA attending the Anti-retroviral Clinic of the University of Port Harcourt Teaching Hospital, were consecutively selected. A questionnaire, administered at interview was used to obtain socio-demographic and medical data. The WHOQOL-HN bref was used to assess the quality of life of each study participant.Results: The mean age ofthe respondents was 37.67 ± 12.1years (range 18-70 years). Two hundred and fifty-six (53%)of the participants were males. 269 (53.8%) were married and 216(80.2%) had spouses who were positive. The QOL mean scores were highest for the environment domain (18.49 ± 2.09) and spirituality I religion I personal beliefs domain (15.52 ± 1.41). Physical health (13.13 ± 1. 70) and psychological domain (13.35 ± 1.31) had QOL mean scores which were similar. The overall QOL mean scores were lowest in social relationships (12.64 ± 2.17) and level of dependence domains (12.69 + 1.30). A significant difference in the mean QOL scores was observed among men (12.87 ± 1.04) compared to women (12.48 ± 1.46) in the level of dependence (p=O.OO).Conclusion: The lower mean score in social relationship and level of dependence domain may suggest the fear of stigmatization and discrimination. Any intervention targeted at improving the quality of life among this group must address this fear. Keywords: PLWHA; Quality of life; WHOQOL-HNbref; South-South; Nigeria.

Background There is increasing evidence that Parkinson's disease (PD) can cause depression. This dimension has not been sufficiently studied particularly among Nigerian Africans. Our aim was to determine the frequency and severity of depression among patients with PD and to compare this with their healthy counterparts.Methods 36 conservative patients with a clinical diagnosis of PD had the Beck Depression Inventory-Il administered to them. A structured questionnaire interview and a neurological examination including the Hoehn and Yahr stage of illness scale and the motor section of the Unified Parkinson's Disease Rating Scale were performed. An equal number of age and sex matched controls were also recruited for the study.Results Of the 36 PD patients, 83.3% had persistently low mood. Based on their Beck Depression Inventory score, 25% had mild depression, 18% had moderate depression and 16.7% had severe depression. Depression was worse with disease severity.Conclusion Patients with PD had a higher frequency of depression compared to their healthy counterparts. A multidisciplinary approach to the management of PD that includes depression-reducing interventions is required for this population of patients.Keywords: Depression, Parkinson's disease, BDI-II

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INTRODUCTION: The Mean platelet volume and platelet counts are indicators of thrombotic potentials, and risk factors for microvascular complications in diabetics. This study aimed to establish variations in platelet counts and mean platelet volume in type 2 diabetic patients on treatment and non-diabetic controls. METHODS: This was an unmatched case-control study involving 200 participants consisting of 100 diabetics and 100 non-diabetic controls. Four and half milliliters of blood was collected from diabetics and non diabetic controls into EDTA anticoagulant tubes. Full blood count was performed using the Sysmex KN-21N, (manufactured by Sysmex corporation Kobe, Japan) a three- part auto analyzer able to run 19 parameters per sample including platelet counts and mean platelet volume. RESULTS: The mean fasting blood sugar for the diabetics was 147.85±72.54 mg/dl and the controls 95.20±30.10 mg/dl. The mean platelet count for the diabetics was 235.29±76.81*109/L and controls, 211.32±66.44*109/L. The mean platelet volume, for the diabetics was 8.69±0.67 fl and the controls, 8.91±0.80 fl. There was a statistically significant difference in platelet counts of diabetics and healthy controls p =0.038 while none existed between the mean platelet volume in diabetics and healthy controls p=0.593. CONCLUSION: This study revealed a higher mean platelet count for diabetics on treatment than for non diabetic controls while mean platelet volume was lower in cases than controls. However, both parameters in diabetics on treatment were within the normal reference range for healthy individuals.

Background: Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards the realization of the global application of precision medicine. The African and African admixed populations enable mapping of complex traits given their greater levels of genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns., Methods: Here we perform a comprehensive genome-wide assessment of Parkinson's disease (PD) in 197,918 individuals (1,488 cases; 196,430 controls) of African and African admixed ancestry, characterizing population-specific risk, differential haplotype structure and admixture, coding and structural genetic variation and polygenic risk profiling., Findings: We identified a novel common risk factor for PD and age at onset at the GBA1 locus (risk, rs3115534-G; OR=1.58, 95% CI = 1.37 - 1.80, P=2.397E-14; age at onset, BETA =-2.004, SE =0.57, P = 0.0005), that was found to be rare in non-African/African admixed populations. Downstream short- and long-read whole genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. However, we identified that this signal mediates PD risk via expression quantitative trait locus (eQTL) mechanisms. While previously identified GBA1 associated disease risk variants are coding mutations, here we suggest a novel functional mechanism consistent with a trend in decreasing glucocerebrosidase activity levels. Given the high population frequency of the underlying signal and the phenotypic characteristics of the homozygous carriers, we hypothesize that this variant may not cause Gaucher disease. Additionally, the prevalence of Gaucher's disease in Africa is low., Interpretation: The present study identifies a novel African-ancestry genetic risk factor in GBA1 as a major mechanistic basis of PD in the African and African admixed populations. This striking result contrasts to previous work in Northern European populations, both in terms of mechanism and attributable risk. This finding highlights the importance of understanding population-specific genetic risk in complex diseases, a particularly crucial point as the field moves toward precision medicine in PD clinical trials and while recognizing the need for equitable inclusion of ancestrally diverse groups in such trials. Given the distinctive genetics of these underrepresented populations, their inclusion represents a valuable step towards insights into novel genetic determinants underlying PD etiology. This opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk., Evidence Before This Study: Our current understanding of Parkinson's disease (PD) is disproportionately based on studying populations of European ancestry, leading to a significant gap in our knowledge about the genetics, clinical characteristics, and pathophysiology in underrepresented populations. This is particularly notable in individuals of African and African admixed ancestries. Over the last two decades, we have witnessed a revolution in the research area of complex genetic diseases. In the PD field, large-scale genome-wide association studies in the European, Asian, and Latin American populations have identified multiple risk loci associated with disease. These include 78 loci and 90 independent signals associated with PD risk in the European population, nine replicated loci and two novel population-specific signals in the Asian population, and a total of 11 novel loci recently nominated through multi-ancestry GWAS efforts.Nevertheless, the African and African admixed populations remain completely unexplored in the context of PD genetics., Added Value of This Study: To address the lack of diversity in our research field, this study aimed to conduct the first genome-wide assessment of PD genetics in the African and African admixed populations. Here, we identified a genetic risk factor linked to PD etiology, dissected African-specific differences in risk and age at onset, characterized known genetic risk factors, and highlighted the utility of the African and African admixed risk haplotype substructure for future fine-mapping efforts. We identified a novel disease mechanism via expression changes consistent with decreased GBA1 activity levels. Future large scale single cell expression studies should investigate the neuronal populations in which expression differences are most prominent. This novel mechanism may hold promise for future efficient RNA-based therapeutic strategies such as antisense oligonucleotides or short interfering RNAs aimed at preventing and decreasing disease risk. We envisage that these data generated under the umbrella of the Global Parkinson's Genetics Program (GP2) will shed light on the molecular mechanisms involved in the disease process and might pave the way for future clinical trials and therapeutic interventions. This work represents a valuable resource in an underserved population, supporting pioneering research within GP2 and beyond. Deciphering causal and genetic risk factors in all these ancestries will help determine whether interventions, potential targets for disease modifying treatment, and prevention strategies that are being studied in the European populations are relevant to the African and African admixed populations., Implications of All the Available Evidence: We nominate a novel signal impacting GBA1 as the major genetic risk factor for PD in the African and African admixed populations. The present study could inform future GBA1 clinical trials, improving patient stratification. In this regard, genetic testing can help to design trials likely to provide meaningful and actionable answers. It is our hope that these findings may ultimately have clinical utility for this underrepresented population.

Background: The microtubule-associated protein tau ( MAPT ) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson's disease (PD). However, there is a lack of clarity regarding the link between the main H1 haplotype and risk of PD. Inconsistencies in reported association may be driven by genetic variability in the populations studied to date. Data on MAPT haplotype frequencies in the general population and association studies exploring the role of MAPT haplotypes in conferring PD risk in black Africans are lacking., Objectives: To determine the frequencies of MAPT haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans., Methods: The haplotype and genotype frequencies of MAPT rs1052553 were analysed using PCR-based KASP™ in 907 individuals with PD and 1,022 age-matched neurologically normal controls from the Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related to PD included age at study, age at onset, and disease duration., Results: The frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and age at onset (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23)., Conclusions: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, the MAPT H1 haplotype was not associated with an increased risk or age at onset of PD.