Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

This study utilized summary statistics of the phase-1 GWAS data from the International FTD-Genomics Consortium (IFGC), comprised of 2,154 clinically diagnosed FTD spectrum cases and 4,308 controls and a total of 6,026,384 SNPs. Of the 2,154 cases diagnosed with FTD, 361 were diagnosed with the svPPA subtype (referred to as “semantic dementia” in the original study). Cases within the cohort were diagnosed according to the Neary criteria for FTLD¹². For additional cohort details, please see Ferrari et al.⁶.

We generated gene-based p-values for 17,466 genes with data available in the svPPA cohort using the tool versatile gene-based association study (VEGAS). We next generated protein interaction networks (PINs) for the significant genes (VEGAS p < 0.05) using the protein interaction network-based pathway analysis (PINBPA) package. The background PIN database used in our analyses…