MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies

Catherine Labbé, Michael G. Heckman, Oswaldo Lorenzo-Betancor, Alexandra I. Soto-Ortolaza, Ronald L. Walton, Melissa E Murray, Mariet Allen, Ryan J. Uitti, Zbigniew K Wszolek, Glenn E. Smith, Kejal M Kantarci, David S Knopman, Val Lowe, Clifford R Jr. Jack, Nilufer Taner, Anhar Hassan, Rodolfo Savica, Ronald Carl Petersen, Joseph E Parisi, Demetrius M. MaraganoreNeill R Graff Radford, Tanis Jill Ferman, Bradley F Boeve, Dennis W Dickson, Owen A Ross

Research output: Contribution to journalArticle

16 Scopus citations


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.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
StateAccepted/In press - 2016



  • Dementia with Lewy bodies
  • Genetic association study
  • Lewy body disease
  • MAPT
  • Tau protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy

Cite this