Genome-wide analysis of the parkinsonism-dementia complex of Guam

Huw R. Morris, John C. Steele, Richard Crook, Fabienne Wavrant-De Vrièze, Luisa Onstead-Cardinale, Katrina Gwinn-Hardy, Nick W. Wood, Matthew Farrer, Andrew J. Lees, P. L. McGeer, Teepu Siddique, John Hardy*, Jordi Perez-Tur

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background: Parkinsonism-dementia complex (PDC) is a neurofibrillary tangle degeneration involving the deposition of Alzheimer-type tau, predominantly in the mesial temporal cortex, brainstem, and basal ganglia. It occurs in focal geographic isolates, including Guam and the Kii peninsula of Japan. The familial clustering of the disease has suggested that a genetic factor could be important in its etiology. Objective: To determine whether a genetic locus could be identified, linked, or associated with PDC. Design and Patients: We performed a genome-wide association study of 22 Guamanian PDC and 19 control subjects using 834 microsatellite markers with an approximate genome-wide marker density of 4.4 centimorgans. Results: Two-point association analysis identified 17 markers (P<.015). Each of these markers then underwent conventional linkage analysis in 5 families with PDC. One marker, D20S103, generated a logarithm of odds score of greater than 1.5. Multipoint association analysis also highlighted 2 other areas on chromosome 14q (adjacent to D14S592, 59.2 megabases [M]) and chromosome 20 (adjacent to D20S470, 17.4 M) with multipoint association logarithm of the odds scores of greater than 2. The areas around D20S103, D14S592, and D20S470 were further analyzed by association using additional microsatellite markers and by conventional linkage analysis. This did not provide further evidence for the role of these areas in PDC. Conclusions: This study has not identified a single gene locus for PDC, confirming the impression of a geographic disease isolate with a complex genetic, a genetic/environmental etiology, or a purely environmental etiology.

Original languageEnglish (US)
Pages (from-to)1889-1897
Number of pages9
JournalArchives of Neurology
Volume61
Issue number12
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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