Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.
Ruth ChiaMarya S SabirSara Bandres-CigaSara Saez-AtienzarRegina Hertfelder ReynoldsEmil Karl GustavssonRonald L WaltonSarah AhmedCoralie ViolletJinhui DingMary B MakariousMónica Diez-FairenMakayla K PortleyZalak ShahYevgeniya AbramzonDena G HernandezCornelis BlauwendraatDavid J StoneJohn EicherLaura ParkkinenOlaf AnsorgeLorraine ClarkLawrence S HonigKaren MarderAfina LemstraPeter St George-HyslopElisabet LondosKevin MorganTammaryn LashleyThomas T WarnerZane JaunmuktaneDouglas GalaskoIsabel SantanaPentti J TienariLiisa MyllykangasMinna OinasNigel J CairnsJohn C MorrisGlenda M HallidayVivanna M Van DeerlinJohn Q TrojanowskiMaurizio GrassanoAndrea CalvoGabriele MoraAntonio CanosaGianluca FlorisRyan C BohannanFrancesca BrettZiv Gan OrJoshua T GeigerAnni MoorePatrick MayRejko KrügerDavid S GoldsteinGrisel LopezNahid TayebiEllen Sidranskynull nullLucy Norcliffe-KaufmannJose-Alberto PalmaHoracio KaufmannVikram G ShakkottaiMatthew PerkinsKathy L NewellThomas GasserClaudia SchulteFrancesco LandiErika SalviDaniele CusiEliezer MasliahRonald C KimChad A CarawayEdwin S MonukiMaura BrunettiTed M DawsonLiana S RosenthalMarilyn S AlbertOlga PletnikovaJuan C TroncosoMargaret E FlanaganQinwen MaoEileen H BigioEloy Rodríguez-RodríguezJon InfanteCarmen LageIsabel González-AramburuPascual Sánchez JuanBernardino GhettiJulia KeithSandra E BlackMario MasellisEkaterina RogaevaCharles DuyckaertsAlexis BriceSuzanne LesageGeorgia XiromerisiouMatthew J BarrettBension S TilleySteve GentlemanGiancarlo LogroscinoGeidy E SerranoThomas G BeachIan G McKeithAlan J ThomasJohannes AttemsChristopher M MorrisLaura PalmerSeth LoveClaire TroakesSafa Al-SarrajAngela K HodgesDag AarslandGregory KleinScott M KaiserRandy WoltjerPau PastorLynn M BekrisJames B LeverenzLilah M BesserAmanda KuzmaAlan E RentonAlison Mary GoateDavid A BennettClemens R ScherzerHuw R MorrisRaffaele FerrariDiego AlbaniStuart Pickering-BrownKelley FaberWalter A KukullEstrella Morenas-RodriguezAlberto LleóJuan ForteaDaniel AlcoleaJordi ClarimonMike A NallsLuigi FerruciSusan M ResnickToshiko TanakaTatiana M ForoudNeill R Graff-RadfordZbigniew K WszolekTanis FermanBradley F BoeveJohn A HardyEric J TopolAli TorkamaniAndrew B SingletonMina RytenDennis W DicksonAdriano ChioOwen A RossRaphael J GibbsClifton L DalgardBryan J TraynorSonja W ScholzPublished in: Nature genetics (2021)
The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.