Genome‐Wide Association Study for CSF Aβ42, Tau, and pTau in a Large Multi‐cohort Study to Identify Novel AD Genetic Variants

Background Previous studies have identified more than 20 genetic loci to be associated with AD risk. These reported do not account for all the estimated heritability nor report enough information on undelaying biological mechanism. Genome-wide association of endophenotypes new Alzheimer’s disease. To better understand pathology and identify variants implicated in much larger samples size is needed. We conducted a GWAS Amyloid-beta (Aβ42) tau, phosphorylated tau (ptau) cerebrospinal fluid (CSF) detect novel AD. Methods CSF biomarkers were measured 7282 individuals from 24 different cohorts. Samples genotyped using array technology stringent quality control standards each dataset before combining datasets. Minimum call rate single nucleotide polymorphism (SNP) was 99.85%. SNPs Hardy–Weinberg equilibrium excluded. X-chromosome analyzed verify sex identification. Duplicates cryptic relatedness among tested by pairwise genome-wide estimates proportion identity-by-descent. PLINK used calculate principal component analysis. biomarker levels log10-transformed approximate normal distribution mean standardized zero variability platforms measure proteins levels. One-stage joint-GWAS maximize power our Post-GWAS analyses Colocalization, Madelian Randomization, LD Score Regression, implemented colocalization two potential related signals common causal variant evaluate overlap architecture Biomarkers risk factor Results This study represents one largest multi-cohort biomarkers. Several significant hits found including APOE. Additional are underway. Conclusions Aβ42, ptau well established clear APOE genotype Genetic provide smaller sample case-control helping us mechanism With this we aim