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Complete genomic screen in Parkinson disease: evidence for multiple genes.

Publication ,  Journal Article
Scott, WK; Nance, MA; Watts, RL; Hubble, JP; Koller, WC; Lyons, K; Pahwa, R; Stern, MB; Colcher, A; Hiner, BC; Jankovic, J; Ondo, WG ...
Published in: JAMA
November 14, 2001

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

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Published In

JAMA

DOI

ISSN

0098-7484

Publication Date

November 14, 2001

Volume

286

Issue

18

Start / End Page

2239 / 2244

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Risk Factors
  • Parkinson Disease
  • Middle Aged
  • Microsatellite Repeats
  • Lod Score
  • Ligases
  • Levodopa
  • Humans
  • Genotype
 

Citation

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Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Koller, W. C., Lyons, K., … Pericak-Vance, M. A. (2001). Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA, 286(18), 2239–2244. https://doi.org/10.1001/jama.286.18.2239
Scott, W. K., M. A. Nance, R. L. Watts, J. P. Hubble, W. C. Koller, K. Lyons, R. Pahwa, et al. “Complete genomic screen in Parkinson disease: evidence for multiple genes.JAMA 286, no. 18 (November 14, 2001): 2239–44. https://doi.org/10.1001/jama.286.18.2239.
Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, et al. Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA. 2001 Nov 14;286(18):2239–44.
Scott, W. K., et al. “Complete genomic screen in Parkinson disease: evidence for multiple genes.JAMA, vol. 286, no. 18, Nov. 2001, pp. 2239–44. Pubmed, doi:10.1001/jama.286.18.2239.
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, Slotterbeck B, Booze MW, Ribble RC, Rampersaud E, West SG, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Vance JM, Pericak-Vance MA. Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA. 2001 Nov 14;286(18):2239–2244.
Journal cover image

Published In

JAMA

DOI

ISSN

0098-7484

Publication Date

November 14, 2001

Volume

286

Issue

18

Start / End Page

2239 / 2244

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Risk Factors
  • Parkinson Disease
  • Middle Aged
  • Microsatellite Repeats
  • Lod Score
  • Ligases
  • Levodopa
  • Humans
  • Genotype