Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

Published

Journal Article

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.

Full Text

Duke Authors

Cited Authors

  • Martin, ER; Scott, WK; Nance, MA; Watts, RL; Hubble, JP; Koller, WC; Lyons, K; Pahwa, R; Stern, MB; Colcher, A; Hiner, BC; Jankovic, J; Ondo, WG; Allen, FH; Goetz, CG; Small, GW; Masterman, D; Mastaglia, F; Laing, NG; Stajich, JM; Ribble, RC; Booze, MW; Rogala, A; Hauser, MA; Zhang, F; Gibson, RA; Middleton, LT; Roses, AD; Haines, JL; Scott, BL; Pericak-Vance, MA; Vance, JM

Published Date

  • November 14, 2001

Published In

Volume / Issue

  • 286 / 18

Start / End Page

  • 2245 - 2250

PubMed ID

  • 11710889

Pubmed Central ID

  • 11710889

International Standard Serial Number (ISSN)

  • 0098-7484

Digital Object Identifier (DOI)

  • 10.1001/jama.286.18.2245

Language

  • eng

Conference Location

  • United States