Enhanced Data Pre-processing for the Identification of Alzheimer’s Disease-Associated SNPs

Alzheimer’s Disease (AD) is a complex neurodegenerative disorder that has gained significant attention in scientific research, particularly since the Human Genome Project. Based on twin studies that utilize the resemblance of Alzheimer’s disease risk between pairs of twins, it has been found that the overall heritability of the disease is estimated at 0.58. When shared environmental factors are taken into account, the maximum heritability reaches 0.79. This suggests that approximately 58-79% of the susceptibility to late-onset Alzheimer’s disease can be attributed to genetic factors [[4][1]]. In 2022, it is estimated that AD will affect over 50 million people worldwide, and its economic burden exceeds a trillion US dollars per year. One promising approach is Genome-Wide Association Studies (GWAS), which allow the identification of genetic variants associated with AD susceptibility. Of particular interest are Single Nucleotide Polymorphisms (SNPs), which represent variations in a single nucleotide base in the DNA sequence. In this study, we investigated the association between SNPs and AD susceptibility by applying various quality control (QC) parameters during data pre-processing and rank the SNP associations through mixed linear models-based GWAS implemented in BLUPF90. Our findings indicate that the identified SNPs are located in regions already associated with Alzheimer’s Disease, including non-coding regions. We also investigated the impact of incorporating demographic data into our models. However, the results indicated that the inclusion of such data did not yield any benefits for the model. This study highlights the importance of GWAS in identifying potential genetic risk factors for AD and underscores the need for further research to gain a better understanding of the complex genetic mechanisms underlying this debilitating disease. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by The Sao Paulo Research Foundation. ### 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: 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at [1]: #ref-4