MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies.
The MAPT H1 haplotype has been associated with several neurodegenerative diseases. We were interested in exploring the role of MAPT haplotypic variation in risk of dementia with Lewy bodies (DLB).



We genotyped six MAPT haplotype tagging SNPs and screened 431 clinical DLB cases, 347 pathologically defined high-likelihood DLB cases, and 1049 controls.



We performed haplotypic association tests and detected an association with the protective H2 haplotype in our combined series (odds ratio [OR] = 0.75). We fine-mapped the locus and identified a relatively rare haplotype, H1G, that is associated with an increased risk of DLB (OR = 3.30, P = .0017). This association was replicated in our pathologically defined series (OR = 2.26, P = .035).



These results support a role for H1 and specifically H1G in susceptibility to DLB. However, the exact functional variant at the locus is still unknown, and additional studies are warranted to fully explain genetic risk of DLB at the MAPT locus.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Catherine
C
Labbé
Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Michael G
MG
Heckman
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Oswaldo
O
Lorenzo-Betancor
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Alexandra I
AI
Soto-Ortolaza
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Ronald L
RL
Walton
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Melissa E
ME
Murray
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Mariet
M
Allen
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Ryan J
RJ
Uitti
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Zbigniew K
ZK
Wszolek
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA.
Glenn E
GE
Smith
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Kejal
K
Kantarci
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
David S
DS
Knopman
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Val J
VJ
Lowe
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Clifford R
CR
Jack
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Nilüfer
N
Ertekin-Taner
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Anhar
A
Hassan
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Rodolfo
R
Savica
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Ronald C
RC
Petersen
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Joseph E
JE
Parisi
Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA.
Demetrius M
DM
Maraganore
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Neill R
NR
Graff-Radford
Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
Tanis J
TJ
Ferman
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Bradley F
BF
Boeve
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Dennis W
DW
Dickson
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Mayo Graduate School, Mayo Clinic, Jacksonville, FL, USA. Electronic address: ross.owen@mayo.edu.
Owen A
OA
Ross
D001921:Brain / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D016875:tau Proteins
Dementia with Lewy bodies; Genetic association study; Lewy body disease; MAPT; tau protein