Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy.
Naomi KouriOwen A RossBeth DombroskiCurtis S YounkinDaniel J SerieAlexandra Soto-OrtolazaMatthew BakerNi Cole A FinchHyejin YoonJungsu KimShinsuke FujiokaCatriona A McLeanBernardino GhettiSalvatore SpinaLaura B CantwellMartin R FarlowJordan GrafmanEdward D HueyMi Ryung HanSherry BeecherEvan T GellerHans A KretzschmarSigrun RoeberMarla GearingJorge L JuncosJean Paul G VonsattelVivianna M Van DeerlinMurray GrossmanHoward I HurtigRachel G GrossSteven E ArnoldJohn Q TrojanowskiVirginia M LeeGregor K WenningCharles L WhiteGünter U HöglingerUlrich MüllerBernie DevlinLawrence I GolbeJulia CrookJoseph E ParisiBradley F BoeveKeith A JosephsZbigniew K WszolekRyan J UittiNeill R Graff-RadfordIrene LitvanSteven G YounkinLi-San WangNilüfer Ertekin-TanerRosa RademakersHakon HakonarsenGerard D SchellenbergDennis W DicksonPublished in: Nature communications (2015)
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).