Analysis Proposal
Analysis Question
Can we validate ABCA7 as an Alzheimer's disease genetic risk locus by corroborating its reported GWAS associations, effect sizes, and population-specific risk contributions?
Datasets
GWAS Catalog (NHGRI-EBI)NIAGADS (NIA Genetics of Alzheimer's Disease Data Storage Site)UK Biobank Phenotype BH16.0 AD endpointsLOAD (Late-Onset Alzheimer's Disease) Consortium GWAS meta-analysis
Methods
Systematic GWAS lookup: query GWAS Catalog API for ABCA7 gene boundary variants (chr9:27500000-28500000 GRCh38) with AD/FTD phenotypesStatistical validation: extract odds ratios, 95% CI, p-values, and sample sizes for significant ABCA7 hits (p<5e-8)Cross-database corroboration: verify reported associations against NIAGADS variant-level summary statisticsEffect size heterogeneity analysis: assess population-specific effects (APOE ε4 stratified) and pleiotropy with lipid metabolism traits
Expected Outputs
- List of genome-wide significant ABCA7 variants with allele frequencies, OR, and 95% CI by ancestry
- Quantified confidence score for ABCA7 AD genetic risk locus status (support: high OR + replicated GWAS hits; refute: no independent GWAS signal after APOE adjustment)
- Evidence item count confirming data_in relation provenance from GWAS datasets
- Flagged low-confidence edge if no independent ABCA7 signals survive multiple testing correction