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 × 10?12), 8p12 at lnc-KIF13B-1 , a long non-coding RNA (rs643472; P =3.41 × 10?8), and 2p22 at SOS1 (rs963731; P =1.76 × 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 × 10?7) and MAPT H1c (17q21; rs242557; P =7.91 × 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).