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

Chia R, Sabir MS, Bandres-Ciga S et al.

33589841 PubMed ID
GWAS Study Type
16516 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

CR
Chia R
SM
Sabir MS
BS
Bandres-Ciga S
SS
Saez-Atienzar S
RR
Reynolds RH
GE
Gustavsson E
WR
Walton RL
AS
Ahmed S
VC
Viollet C
DJ
Ding J
MM
Makarious MB
DM
Diez-Fairen M
PM
Portley MK
SZ
Shah Z
AY
Abramzon Y
HD
Hernandez DG
BC
Blauwendraat C
SD
Stone DJ
EJ
Eicher J
PL
Parkkinen L
AO
Ansorge O
CL
Clark L
HL
Honig LS
MK
Marder K
LA
Lemstra A
SG
St George-Hyslop P
LE
Londos E
MK
Morgan K
LT
Lashley T
WT
Warner TT
JZ
Jaunmuktane Z
GD
Galasko D
SI
Santana I
TP
Tienari PJ
ML
Myllykangas L
OM
Oinas M
CN
Cairns NJ
MJ
Morris JC
HG
Halliday GM
VD
Van Deerlin VM
TJ
Trojanowski JQ
GM
Grassano M
CA
Calvo A
MG
Mora G
CA
Canosa A
FG
Floris G
BR
Bohannan RC
BF
Brett F
GZ
Gan-Or Z
GJ
Geiger JT
MA
Moore A
MP
May P
KR
Krüger R
GD
Goldstein DS
LG
Lopez G
TN
Tayebi N
SE
Sidransky E
NL
Norcliffe-Kaufmann L
PJ
Palma JA
KH
Kaufmann H
SV
Shakkottai VG
PM
Perkins M
NK
Newell KL
GT
Gasser T
SC
Schulte C
LF
Landi F
SE
Salvi E
CD
Cusi D
ME
Masliah E
KR
Kim RC
CC
Caraway CA
ME
Monuki ES
BM
Brunetti M
DT
Dawson TM
RL
Rosenthal LS
AM
Albert MS
PO
Pletnikova O
TJ
Troncoso JC
FM
Flanagan ME
MQ
Mao Q
BE
Bigio EH
RE
Rodríguez-Rodríguez E
IJ
Infante J
LC
Lage C
GI
González-Aramburu I
SP
Sanchez-Juan P
GB
Ghetti B
KJ
Keith J
BS
Black SE
MM
Masellis M
RE
Rogaeva E
DC
Duyckaerts C
BA
Brice A
LS
Lesage S
XG
Xiromerisiou G
BM
Barrett MJ
TB
Tilley BS
GS
Gentleman S
LG
Logroscino G
SG
Serrano GE
BT
Beach TG
MI
McKeith IG
TA
Thomas AJ
AJ
Attems J
MC
Morris CM
PL
Palmer L
LS
Love S
TC
Troakes C
AS
Al-Sarraj S
HA
Hodges AK
AD
Aarsland D
KG
Klein G
KS
Kaiser SM
WR
Woltjer R
PP
Pastor P
BL
Bekris LM
LJ
Leverenz JB
BL
Besser LM
KA
Kuzma A
RA
Renton AE
GA
Goate A
BD
Bennett DA
SC
Scherzer CR
MH
Morris HR
FR
Ferrari R
AD
Albani D
PS
Pickering-Brown S
FK
Faber K
KW
Kukull WA
ME
Morenas-Rodriguez E
LA
Lleó A
FJ
Fortea J
AD
Alcolea D
CJ
Clarimon J
NM
Nalls MA
FL
Ferrucci L
RS
Resnick SM
TT
Tanaka T
FT
Foroud TM
GN
Graff-Radford NR
WZ
Wszolek ZK
FT
Ferman T
BB
Boeve BF
HJ
Hardy JA
TE
Topol EJ
TA
Torkamani A
SA
Singleton AB
RM
Ryten M
DD
Dickson DW
CA
Chiò A
RO
Ross OA
GJ
Gibbs JR
DC
Dalgard CL
TB
Traynor BJ
SS
Scholz SW
Chapter II

Abstract

Summary of the research findings

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.

2,591 European ancestry cases, 4,027 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

16516
Total Participants
GWAS
Study Type
Yes
Replicated
970 European ancestry cases, 8,928 European ancestry controls
Replication Participants
European
Ancestry
France, Greece, Italy, Luxembourg, Republic of Ireland, Spain, U.K., Canada, U.S.
Recruitment Country
Chapter IV

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