First GWAS on Alzheimer’s Disease in Argentina and Chile populations

INTRODUCTION Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS we performed a GWAS on sporadic Alzheimer’s disease (AD) including 540 patients and 852 controls from Argentina and Chile. We explored the variants associated with AD in European GWAS from European Alzheimer’s and Dementia Biobank (EADB) and tested their genetic risk score (GRS) performance in this admixed population. RESULTS we detected APOE4 as single genome-wide significant signal (OR=2.93[2.37-3.63], p=2.6×10−23), and fifteen additional suggestive signals previously undetected. Nine of the 83 variants reported by EADB in Europeans were replicated, and the AD-GRS presented similar performance in this Latin population, despite the score diminishes when the Native American ancestry rises. DISCUSSION we report the first GWAS on AD in a population from South America. It shows shared genetics that modulate AD risk between the European and the Latin American populations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by funding from Alexander von Humboldt Foundation to MCD; the Agencia Nacional de Promocion Cientifica y Tecnologica (PID-2011-0059, PIBT/09-2013, PICT-2016-4647 and PICT2019-0656 to LM) and from EU-LAC Health-Neurodegeneration JOINT CALL 2016 (EULACH16 to LM) of Argentina. The Funding of the ALEXANDROS study was provided by the Chilean National Fund for Science and Technology (FONDECYT) grant 1130947. The genotyping for the Chilean series was funded by Genome Research at Ace Alzheimer Center Barcelona project (GR@ACE), supported by Grifols SA, Fundacion bancaria 'La Caixa', Ace Alzheimer Center Barcelona and CIBERNED. The genotyping of Argentinian samples was funded by JPND EADB grant (German Federal Ministry of Education and Research, BMBF: 01ED1619A). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB Fundacion Insituto Leloir (HHS IRB00007572, IORG006295, FWA00020769) gave ethical approval for the protocol CBFIL22. The ethical committee of Institute of Nutrition and Food Technology, University of Chile (Acta 23, 2012) approved the study protocol (FONDECYT 1130947). GWAS study and the FONDAP GERO project 15150012 was approved by the Ethics Committe Servicio de Salud Metropolitano Oriente. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.