MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies.
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ABSTRACT: Introduction
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).Method
We genotyped six MAPT haplotype tagging SNPs and screened 431 clinical DLB cases, 347 pathologically defined high-likelihood DLB cases, and 1049 controls.Result
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).Discussion
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.
SUBMITTER: Labbe C
PROVIDER: S-EPMC5143206 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
Publications
MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies.
Labbé Catherine C Heckman Michael G MG Lorenzo-Betancor Oswaldo O Soto-Ortolaza Alexandra I AI Walton Ronald L RL Murray Melissa E ME Allen Mariet M Uitti Ryan J RJ Wszolek Zbigniew K ZK Smith Glenn E GE Kantarci Kejal K Knopman David S DS Lowe Val J VJ Jack Clifford R CR Ertekin-Taner Nilüfer N Hassan Anhar A Savica Rodolfo R Petersen Ronald C RC Parisi Joseph E JE Maraganore Demetrius M DM Graff-Radford Neill R NR Ferman Tanis J TJ Boeve Bradley F BF Dickson Dennis W DW Ross Owen A OA
Alzheimer's & dementia : the journal of the Alzheimer's Association 20160607 12
<h4>Introduction</h4>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).<h4>Method</h4>We genotyped six MAPT haplotype tagging SNPs and screened 431 clinical DLB cases, 347 pathologically defined high-likelihood DLB cases, and 1049 controls.<h4>Result</h4>We performed haplotypic association tests and detected an association with the protective H2 haplot ...[more]
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