Complete genomic screen in parkinson disease evidence for multiple genes

William K Scott, 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, Christopher G. Goetz, Gary W. Small, Donna Masterman, Frank Mastaglia, Nigel G. Laing, Jeffrey M. Stajich, Brandon SlotterbeckMichael W. Booze, Robert C. Ribble, Evadnie Rampersaud, Sandra G. West, Rachel A. Gibson, Lefkos T. Middleton, Allen D. Roses, Jonathan L. Haines, Burton L. Scott, Jeffery M Vance, Margaret A Pericak-Vance

Research output: Contribution to journalArticle

253 Citations (Scopus)

Abstract

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 individ ual with PD onset at you nger 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.

Original languageEnglish
Pages (from-to)2239-2244
Number of pages6
JournalJournal of the American Medical Association
Volume286
Issue number18
StatePublished - Nov 14 2001
Externally publishedYes

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Parkinson Disease
Genes
Genetic Linkage
Levodopa
Chromosomes
Chromosomes, Human, Pair 6
Twin Studies
Observational Studies
Outcome Assessment (Health Care)
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. Journal of the American Medical Association, 286(18), 2239-2244.

Complete genomic screen in parkinson disease evidence for multiple genes. / Scott, William K; Nance, Martha A.; Watts, Ray L.; Hubble, Jean P.; Koller, William C.; Lyons, Kelly; Pahwa, Rajesh; Stern, Matthew B.; Colcher, Amy; Hiner, Bradley C.; Jankovic, Joseph; Ondo, William G.; Allen, Fred H.; Goetz, Christopher G.; Small, Gary W.; Masterman, Donna; Mastaglia, Frank; Laing, Nigel G.; Stajich, Jeffrey M.; Slotterbeck, Brandon; Booze, Michael W.; Ribble, Robert C.; Rampersaud, Evadnie; West, Sandra G.; Gibson, Rachel A.; Middleton, Lefkos T.; Roses, Allen D.; Haines, Jonathan L.; Scott, Burton L.; Vance, Jeffery M; Pericak-Vance, Margaret A.

In: Journal of the American Medical Association, Vol. 286, No. 18, 14.11.2001, p. 2239-2244.

Research output: Contribution to journalArticle

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 2001, 'Complete genomic screen in parkinson disease evidence for multiple genes', Journal of the American Medical Association, vol. 286, no. 18, pp. 2239-2244.
Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K et al. Complete genomic screen in parkinson disease evidence for multiple genes. Journal of the American Medical Association. 2001 Nov 14;286(18):2239-2244.
Scott, William K ; Nance, Martha A. ; Watts, Ray L. ; Hubble, Jean P. ; Koller, William C. ; Lyons, Kelly ; Pahwa, Rajesh ; Stern, Matthew B. ; Colcher, Amy ; Hiner, Bradley C. ; Jankovic, Joseph ; Ondo, William G. ; Allen, Fred H. ; Goetz, Christopher G. ; Small, Gary W. ; Masterman, Donna ; Mastaglia, Frank ; Laing, Nigel G. ; Stajich, Jeffrey M. ; Slotterbeck, Brandon ; Booze, Michael W. ; Ribble, Robert C. ; Rampersaud, Evadnie ; West, Sandra G. ; Gibson, Rachel A. ; Middleton, Lefkos T. ; Roses, Allen D. ; Haines, Jonathan L. ; Scott, Burton L. ; Vance, Jeffery M ; Pericak-Vance, Margaret A. / Complete genomic screen in parkinson disease evidence for multiple genes. In: Journal of the American Medical Association. 2001 ; Vol. 286, No. 18. pp. 2239-2244.
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title = "Complete genomic screen in parkinson disease evidence for multiple genes",
abstract = "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 individ ual with PD onset at you nger 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.",
author = "Scott, {William K} and Nance, {Martha A.} and Watts, {Ray L.} and Hubble, {Jean P.} and Koller, {William C.} and Kelly Lyons and Rajesh Pahwa and Stern, {Matthew B.} and Amy Colcher and Hiner, {Bradley C.} and Joseph Jankovic and Ondo, {William G.} and Allen, {Fred H.} and Goetz, {Christopher G.} and Small, {Gary W.} and Donna Masterman and Frank Mastaglia and Laing, {Nigel G.} and Stajich, {Jeffrey M.} and Brandon Slotterbeck and Booze, {Michael W.} and Ribble, {Robert C.} and Evadnie Rampersaud and West, {Sandra G.} and Gibson, {Rachel A.} and Middleton, {Lefkos T.} and Roses, {Allen D.} and Haines, {Jonathan L.} and Scott, {Burton L.} and Vance, {Jeffery M} and Pericak-Vance, {Margaret A}",
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T1 - Complete genomic screen in parkinson disease evidence for multiple genes

AU - Scott, William K

AU - Nance, Martha A.

AU - Watts, Ray L.

AU - Hubble, Jean P.

AU - Koller, William C.

AU - Lyons, Kelly

AU - Pahwa, Rajesh

AU - Stern, Matthew B.

AU - Colcher, Amy

AU - Hiner, Bradley C.

AU - Jankovic, Joseph

AU - Ondo, William G.

AU - Allen, Fred H.

AU - Goetz, Christopher G.

AU - Small, Gary W.

AU - Masterman, Donna

AU - Mastaglia, Frank

AU - Laing, Nigel G.

AU - Stajich, Jeffrey M.

AU - Slotterbeck, Brandon

AU - Booze, Michael W.

AU - Ribble, Robert C.

AU - Rampersaud, Evadnie

AU - West, Sandra G.

AU - Gibson, Rachel A.

AU - Middleton, Lefkos T.

AU - Roses, Allen D.

AU - Haines, Jonathan L.

AU - Scott, Burton L.

AU - Vance, Jeffery M

AU - Pericak-Vance, Margaret A

PY - 2001/11/14

Y1 - 2001/11/14

N2 - 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 individ ual with PD onset at you nger 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.

AB - 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 individ ual with PD onset at you nger 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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