Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

摘要

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n = 152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P = 1.42 x 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P = 3.41 x 10(-8)), and 2p22 at SOS1 (rs963731; P = 1.76 x 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P = 2.07 x 10(-7)) and MAPT H1c (17q21; rs242557; P = 7.91 x 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).