Genetic architecture of plasma Alzheimer’s disease biomarkers

Background Case-control genome-wide association studies (GWAS) have identified loci associated with risk for Alzheimer disease (AD), but they require very large sample sizes and identify variants small effect sizes. GWAS of informative endophenotypes more power to novel provide information about biological mechanisms. By analyzing data from 1,269 individuals, we previously AD that were CSF levels tau p-tau, including a variant risk. Recent technological developments led new assays in plasma Aβ, p-tau NFL high predictive power. However, no been performed using these biomarkers as quantitative trait. Method Plasma Aβ obtained 882 individuals the Knight-ADRC, Aß 160 Human Connectome Project, Aß, NFL, 1,694 ADNI. sequencing is also available samples. We linear regression determine single nucleotide polymorphisms (SNPs) biomarkers. SKAT-O was used perform gene-based analyses rare non-synonymous variants. GCTA LDSC proportion biomarker variability explained by genetic colocalization if are risk, onset or progression. Mendelian randomization overlap architecture other traits, cardiovascular inflammation-related traits. Result This represents largest measured powerful assays. found several significant hits, APOE. Additional ongoing. Conclusion Previous traits genes implicated current study can be critical identification impact accurate interpretation levels.