, Volume 5, Issue 3, pp 147–155 | Cite as

Linkage disequilibrium and haplotype tagging polymorphisms in the Tau H1 haplotype

  • Sofia A. Oliveira
  • William K. Scott
  • Fengyu Zhang
  • Jeffrey M. Stajich
  • Kenichiro Fujiwara
  • Michael Hauser
  • Burton L. Scott
  • Margaret A. Pericak-Vance
  • Jeffery M. Vance
  • Eden R. Martin
Original Article


We and others have previously detected association of the Tau H1 haplotype on chromosome 17 with risk of idiopathic Parkinson disease (PD). The H1 haplotype appears to have a fundamental importance in neurodegeneration, as multiple studies have shown it is also associated with an increased risk for progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration syndromes, and primary progressive aphasia. Therefore, to divide the H1 haplotype into sub-haplotypes that could be more significantly associated with the risk of developing PD, and to delimit the genes lying in the H1 haplotype, we analyzed 34 single nucleotide polymorphisms (SNPs) spanning over 3.15 megabases in the region containing Tau. These SNPs are located in or flank the corticotropin-releasing hormone receptor 1, presenilin homolog 2, Tau, Saitohin, and KIAA1267 genes. Analysis of linkage disequilibrium (LD) using these 34 SNPs suggests that the H1 haplotype extends over about 1.3 megabases, making it the largest region of LD reported to date. Of the 29 SNPs lying in this region of LD, 5 were identified as “haplotype tagging” SNPs (htSNPs), capturing 96% of the sample’s haplotype diversity. Association analysis with these htSNPs revealed a new H1 sub-haplotype that is significantly associated with PD (P<0.02). These results define the genes and regulatory regions included in this region of LD, containing an important susceptibility allele contributing to increased risk of neurodegeneration.


Tau H1 haplotype Linkage disequilibrium Haplotype tagging polymorphisms Parkinson disease 



We are grateful to all of the families whose participation made this project possible. We thank the members of the PD Genetics Collaboration Martha A. Nance, Ray L. Watts, Jean P. Hubble, William C. Koller, Kelly Lyons, Rajesh Pahwa, Matthew B. Stern, Amy Colcher, Bradley C. Hiner, Joseph Jankovic, William G. Ondo, Fred H. Allen Jr, Christopher G. Goetz, Gary W. Small, Donna Masterman, Frank Mastaglia, and Jonathan L. Haines who contributed families to the study. We also thank Drs. Richard Morris and Norman Kaplan for their review of this manuscript and helpful comments, and the personnel at the Center for Human Genetics, Duke University Medical Center. This research was supported in part by the Morris K. Udall Parkinson’s Disease Research Center of Excellence grant 5 P50 NS39764. Additional funding was received from the National Institute on Aging (1R01-AG-20135–01) and GlaxoSmithKline. S.A.O. receives funding from a post-doctoral fellowship (BPD/5733/2001) granted by the Portuguese Science and Technology Foundation (FCT).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Sofia A. Oliveira
    • 1
    • 2
  • William K. Scott
    • 1
    • 2
  • Fengyu Zhang
    • 1
    • 2
  • Jeffrey M. Stajich
    • 1
    • 2
  • Kenichiro Fujiwara
    • 1
    • 2
  • Michael Hauser
    • 1
    • 2
  • Burton L. Scott
    • 1
    • 2
  • Margaret A. Pericak-Vance
    • 1
    • 2
  • Jeffery M. Vance
    • 1
    • 2
  • Eden R. Martin
    • 1
    • 2
    • 3
  1. 1.Department of MedicineDuke University Medical CenterDurhamUSA
  2. 2.Center for Human GeneticsDuke University Medical CenterDurhamUSA
  3. 3.Duke University Medical CenterDurhamUSA

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