There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Krishna Kalari |
| Institution: | Mayo Clinic |
| Department: | Quantitative Health Sciences |
| Country: | |
| Proposed Analysis: | BACKGROUND Several groups have shown sex-specific differential gene expression response to AD pathology. However, germline sex chromosome data have often been neglected in genome-wide association studies (GWAS), despite sex chromosome (chrX and chrY) variants being assayed on the Affymetrix/Illumina chips. There are more than 2000 genes on sex chromosomes, and several of those genes are related to inflammation and other metabolic pathways. Even the recent (Bellenguez et al., 2022) largest Alzheimer's disease (111,326 ADD cases and 677,663 controls) case-control study conducted thus far have a missed opportunity to evaluate chrX and Y. In this proposal, we will specifically investigate single nucleotide polymorphisms (SNPs) related to sex and the autosomal chromosomes to identify the genetic risk of Alzheimer's disease. PRELIMINARY DATA The NHGRI-EBI GWAS catalog is a publicly available database where germline-disease associations are stored. As of February 2022, 5617 publications with 345,744 SNP-trait associations were deposited in the NHGRI-EBI GWAS catalog. For Alzheimer's disease, the GWAS catalog database consists of 1697 unique associations pooled from 135 GWAS studies. Of those associations, only 2 SNPs are associated with chrX, which shows the negligence of sex chromosomes during the analysis. Even chromosome 21 (48 Mb), which is 1/3 the size of chromosome X (155 Mb), has four times more associations for diseases in the GWAS catalog. Similarly, 19 polygenic score models in the PGS catalog are associated with Alzheimer's disease. The 19 PGS models, on average, consist of 20 SNPs/model. However, like the GWAS catalog, only 2 SNPs in PGS models belong to chromosome X. We and others have shown that selecting sensible algorithms and parameter settings, including chromosome X and Y in GWAS, is manageable. Closing this computational gap is expected to elucidate complex diseases' genetic backgrounds, especially those with sex-specific features. DATA REQUEST We request the genotyping data of ADNI-1, ADNI GO/2 and ADNI WGS cohorts data. Specifically we request the SNPs from Chromosome X and Y along with autosomal SNP data. We also request processed FDG-PET data for all the samples in this cohort. ANALYSIS PLAN We will conduct association of SNPs specifically from chromosome X and Y along with autosomal SNPs to determine the genes/SNPs or loci associated with brain gap index in males and females separately. Our goal is to determine the genes/pathways associated with Alzheimers disease and prioritize the candidates for conducting mechanistic studies. |
| Additional Investigators |
