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Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda
  1. Anne Stevenson1,2,
  2. Dickens Akena3,
  3. Rocky E Stroud1,2,
  4. Lukoye Atwoli4,
  5. Megan M Campbell5,
  6. Lori B Chibnik1,2,
  7. Edith Kwobah6,
  8. Symon M Kariuki7,8,
  9. Alicia R Martin2,9,
  10. Victoria de Menil1,2,
  11. Charles R J C Newton7,8,
  12. Goodman Sibeko5,
  13. Dan J Stein5,10,
  14. Solomon Teferra11,
  15. Zukiswa Zingela12,
  16. Karestan C Koenen1,2
  1. 1 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  2. 2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  3. 3 Department of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
  4. 4 Department of Mental Health, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya
  5. 5 University of Cape Town, Department of Psychiatry and Mental Health, Cape Town, South Africa
  6. 6 Department of Mental Health, Moi Teaching and Referral Hospital, Eldoret, Kenya
  7. 7 Neurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
  8. 8 Department of Psychiatry, Oxford University, Oxford, UK
  9. 9 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
  10. 10 SA MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa
  11. 11 Department of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
  12. 12 Department of Psychiatry and Human Behavioral Sciences, Walter Sisulu University, Mthatha, Eastern Cape, South Africa
  1. Correspondence to Anne Stevenson; astevens{at}broadinstitute.org

Abstract

Introduction Schizophrenia and bipolar disorder account for a large proportion of the global burden of disease. Despite their enormous impact, little is known about their pathophysiology. Given the high heritability of schizophrenia and bipolar disorder, unbiased genetic studies offer the opportunity to gain insight into their neurobiology. However, advances in understanding the genetic architecture of schizophrenia and bipolar disorder have been based almost exclusively on subjects of Northern European ancestry. The Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) project aims to expand our understanding of the causes of schizophrenia and bipolar disorder through large-scale sample collection and analyses in understudied African populations.

Methods and analysis NeuroGAP-Psychosis is a case-control study of 34 000 participants recruited across multiple sites within Ethiopia, Kenya, South Africa and Uganda. Participants will include individuals who are at least 18 years old with a clinical diagnosis of schizophrenia or bipolar disorder (‘psychosis’) or those with no history of psychosis. Research assistants will collect phenotype data and saliva for DNA extraction. Data on mental disorders, history of physical health problems, substance use and history of past traumatic events will be collected from all participants.

DNA extraction will take place in-country, with genotyping performed at the Broad Institute. The primary analyses will include identifying major groups of participants with similar ancestry using the computation-efficient programme single nucleotide polymorphisms (SNP) weights. This will be followed by a GWAS within and across ancestry groups.

Ethics and dissemination All participants will be assessed for capacity to consent using the University of California, San Diego Brief Assessment of Capacity to Consent. Those demonstrating capacity to consent will be required to provide informed consent. Ethical clearances to conduct this study have been obtained from all participating sites. Findings from this study will be disseminated in publications and shared with controlled access public databases, such as the database of Genotypes and Phenotypes, dbGaP.

  • genetics
  • mental Health
  • Africa

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Footnotes

  • Patient consent for publication Not required.

  • AS and DA contributed equally.

  • Contributors KCK, DS: conceptualised and designed the study. AS, DA, RES, LA, EK, SMK, VdM, CRJCN, DS, ST, ZZ, KCK: wrote the protocol, selected the phenotype questionnaires and added site-specific information. LC, ARM: wrote the sample size, power calculations and statistical analysis plans. MMC, GS: contributed to the UBACC process. AS, DA: wrote the draft of the manuscript and incorporated the revisions by the co-authors; they contributed equally to this paper. All authors reviewed the manuscript for intellectual content, contributed to revisions and approved the final version for publication.

  • Funding This study is funded by the Stanley Center for Psychiatric Research at Broad Institute. The sponsor was involved in the study design, in the writing of the report and in the decision to submit the paper for publication. The sponsor will be involved in the analysis and interpretation of the data. ARM was supported by funding from the National Institutes of Health (K99MH117229).

  • Competing interests DS has received research grants and/or consultancy honoraria from Biocodex, Lundbeck, Servier and Sun.

  • Ethics approval Ethical clearances to conduct this study have been obtained from all participating sites, including: Ethiopia: Addis Ababa University College of Health Sciences (#014/17/Psy) and the Ministry of Science and Technology National Research Ethics Review Committee (#3.10/14/2018). Kenya: Moi University School of Medicine Institutional Research and Ethics Committee (#IREC/2016/145, approval number: IREC 1727), Kenya National Council of Science and Technology (#NACOSTI/P/17/56302/19576) KEMRI Centre Scientific Committee (CSC# KEMRI/CGMRC/CSC/070/2016), KEMRI Scientific and Ethics Review Unit (SERU#KEMRI/SERU/CGMR-C/070/3575). South Africa: The University of Cape Town Human Research Ethics Committee (#466/2016) and Walter Sisulu University Research and Ethics Committee (# 051/2016). Uganda: The Makerere University School of Medicine Research and Ethics Committee (SOMREC #REC REF 2016-057) and the Uganda National Council for Science and Technology (UNCST #HS14ES). USA: The Harvard T.H. Chan School of Public Health (#IRB17-0822).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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