Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.

  • Transversal Translational Medicine
February 15, 2021 By:
  • Chia R
  • Sabir MS
  • Bandres-Ciga S
  • Saez-Atienzar S
  • Reynolds RH
  • Gustavsson E
  • Walton RL
  • Ahmed S
  • Viollet C
  • Ding J
  • Makarious MB
  • Diez-Fairen M
  • Portley MK
  • Shah Z
  • Abramzon Y
  • Hernandez DG
  • Blauwendraat C
  • Stone DJ
  • Eicher J
  • Parkkinen L
  • Ansorge O
  • Clark L
  • Honig LS
  • Marder K
  • Lemstra A
  • St George-Hyslop P
  • Londos E
  • Morgan K
  • Lashley T
  • Warner TT
  • Jaunmuktane Z
  • Galasko D
  • Santana I
  • Tienari PJ
  • Myllykangas L
  • Oinas M
  • Cairns NJ
  • Morris JC
  • Halliday GM
  • Van Deerlin VM
  • Trojanowski JQ
  • Grassano M
  • Calvo A
  • Mora G
  • Canosa A
  • Floris G
  • Bohannan RC
  • Brett F
  • Gan-Or Z
  • Geiger JT
  • Moore A
  • May P
  • Kruger R
  • Goldstein DS
  • Lopez G
  • Tayebi N
  • Sidransky E
  • American Genome C
  • Norcliffe-Kaufmann L
  • Palma JA
  • Kaufmann H
  • Shakkottai VG
  • Perkins M
  • Newell KL
  • Gasser T
  • Schulte C
  • Landi F
  • Salvi E
  • Cusi D
  • Masliah E
  • Kim RC
  • Caraway CA
  • Monuki ES
  • Brunetti M
  • Dawson TM
  • Rosenthal LS
  • Albert MS
  • Pletnikova O
  • Troncoso JC
  • Flanagan ME
  • Mao Q
  • Bigio EH
  • Rodriguez-Rodriguez E
  • Infante J
  • Lage C
  • Gonzalez-Aramburu I
  • Sanchez-Juan P
  • Ghetti B
  • Keith J
  • Black SE
  • Masellis M
  • Rogaeva E
  • Duyckaerts C
  • Brice A
  • Lesage S
  • Xiromerisiou G
  • Barrett MJ
  • Tilley BS
  • Gentleman S
  • Logroscino G
  • Serrano GE
  • Beach TG
  • McKeith IG
  • Thomas AJ
  • Attems J
  • Morris CM
  • Palmer L
  • Love S
  • Troakes C
  • Al-Sarraj S
  • Hodges AK
  • Aarsland D
  • Klein G
  • Kaiser SM
  • Woltjer R
  • Pastor P
  • Bekris LM
  • Leverenz JB
  • Besser LM
  • Kuzma A
  • Renton AE
  • Goate A
  • Bennett DA
  • Scherzer CR
  • Morris HR
  • Ferrari R
  • Albani D
  • Pickering-Brown S
  • Faber K
  • Kukull WA
  • Morenas-Rodriguez E
  • Lleo A
  • Fortea J
  • Alcolea D
  • Clarimon J
  • Nalls MA
  • Ferrucci L
  • Resnick SM
  • Tanaka T
  • Foroud TM
  • Graff-Radford NR
  • Wszolek ZK
  • Ferman T
  • Boeve BF
  • Hardy JA
  • Topol EJ
  • Torkamani A
  • Singleton AB
  • Ryten M
  • Dickson DW
  • Chio A
  • Ross OA
  • Gibbs JR
  • Dalgard CL
  • Traynor BJ
  • Scholz SW.

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.

2021 Feb. Nat Genet. Online ahead of print.
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