TY - JOUR
T1 - MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies
AU - Labbé, Catherine
AU - Heckman, Michael G.
AU - Lorenzo-Betancor, Oswaldo
AU - Soto-Ortolaza, Alexandra I.
AU - Walton, Ronald L.
AU - Murray, Melissa E.
AU - Allen, Mariet
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew K.
AU - Smith, Glenn E.
AU - Kantarci, Kejal
AU - Knopman, David S.
AU - Lowe, Val J.
AU - Jack, Clifford R.
AU - Ertekin-Taner, Nilüfer
AU - Hassan, Anhar
AU - Savica, Rodolfo
AU - Petersen, Ronald C.
AU - Parisi, Joseph E.
AU - Maraganore, Demetrius M.
AU - Graff-Radford, Neill R.
AU - Ferman, Tanis J.
AU - Boeve, Bradley F.
AU - Dickson, Dennis W.
AU - Ross, Owen A.
N1 - Publisher Copyright:
© 2016 the Alzheimer's Association
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Dementia with Lewy bodies
KW - Genetic association study
KW - Lewy body disease
KW - MAPT
KW - tau protein
UR - http://www.scopus.com/inward/record.url?scp=84979529867&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979529867&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2016.05.002
DO - 10.1016/j.jalz.2016.05.002
M3 - Article
C2 - 27287057
AN - SCOPUS:84979529867
SN - 1552-5260
VL - 12
SP - 1297
EP - 1304
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 12
ER -