PARK3 influences age at onset in Parkinson disease: A genome scan in the GenePD study

Anita L. DeStefano, Mark F. Lew, Lawrence Golbe, Margery Mark, Alice M. Lazzarini, Mark Guttman, Erwin Montgomery, Cheryl H. Waters, Carlos Singer, Ray L. Watts, Lillian J. Currie, G. Frederick Wooten, Nancy E. Maher, Jemma B. Wilk, Kristin M. Sullivan, Karen M. Slater, Marie H. Saint-Hilaire, Robert G. Feldman, Oksana Suchowersky, Anne Louise LafontaineNancy Labelle, John H. Growdon, Peter Vieregge, Peter P. Pramstaller, Christine Klein, Jean P. Hubble, Carson R. Reider, Mark Stacy, Marcy E. MacDonald, James F. Gusella, Richard H. Myers

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Abstract

Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: Chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P =. 02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.

Original languageEnglish (US)
Pages (from-to)1089-1095
Number of pages7
JournalAmerican Journal of Human Genetics
Volume70
Issue number5
DOIs
StatePublished - Jan 1 2002

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Parkinson Disease
Genome
Chromosomes
Alleles
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 21
Disease Susceptibility
Linkage Disequilibrium
Parkinsonian Disorders
Age of Onset
Neurodegenerative Diseases
Haplotypes
Genes
Analysis of Variance
Parkinson Disease 10
Mutation
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

DeStefano, A. L., Lew, M. F., Golbe, L., Mark, M., Lazzarini, A. M., Guttman, M., ... Myers, R. H. (2002). PARK3 influences age at onset in Parkinson disease: A genome scan in the GenePD study. American Journal of Human Genetics, 70(5), 1089-1095. https://doi.org/10.1086/339814
DeStefano, Anita L. ; Lew, Mark F. ; Golbe, Lawrence ; Mark, Margery ; Lazzarini, Alice M. ; Guttman, Mark ; Montgomery, Erwin ; Waters, Cheryl H. ; Singer, Carlos ; Watts, Ray L. ; Currie, Lillian J. ; Wooten, G. Frederick ; Maher, Nancy E. ; Wilk, Jemma B. ; Sullivan, Kristin M. ; Slater, Karen M. ; Saint-Hilaire, Marie H. ; Feldman, Robert G. ; Suchowersky, Oksana ; Lafontaine, Anne Louise ; Labelle, Nancy ; Growdon, John H. ; Vieregge, Peter ; Pramstaller, Peter P. ; Klein, Christine ; Hubble, Jean P. ; Reider, Carson R. ; Stacy, Mark ; MacDonald, Marcy E. ; Gusella, James F. ; Myers, Richard H. / PARK3 influences age at onset in Parkinson disease : A genome scan in the GenePD study. In: American Journal of Human Genetics. 2002 ; Vol. 70, No. 5. pp. 1089-1095.
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abstract = "Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: Chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P =. 02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.",
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DeStefano, AL, Lew, MF, Golbe, L, Mark, M, Lazzarini, AM, Guttman, M, Montgomery, E, Waters, CH, Singer, C, Watts, RL, Currie, LJ, Wooten, GF, Maher, NE, Wilk, JB, Sullivan, KM, Slater, KM, Saint-Hilaire, MH, Feldman, RG, Suchowersky, O, Lafontaine, AL, Labelle, N, Growdon, JH, Vieregge, P, Pramstaller, PP, Klein, C, Hubble, JP, Reider, CR, Stacy, M, MacDonald, ME, Gusella, JF & Myers, RH 2002, 'PARK3 influences age at onset in Parkinson disease: A genome scan in the GenePD study', American Journal of Human Genetics, vol. 70, no. 5, pp. 1089-1095. https://doi.org/10.1086/339814

PARK3 influences age at onset in Parkinson disease : A genome scan in the GenePD study. / DeStefano, Anita L.; Lew, Mark F.; Golbe, Lawrence; Mark, Margery; Lazzarini, Alice M.; Guttman, Mark; Montgomery, Erwin; Waters, Cheryl H.; Singer, Carlos; Watts, Ray L.; Currie, Lillian J.; Wooten, G. Frederick; Maher, Nancy E.; Wilk, Jemma B.; Sullivan, Kristin M.; Slater, Karen M.; Saint-Hilaire, Marie H.; Feldman, Robert G.; Suchowersky, Oksana; Lafontaine, Anne Louise; Labelle, Nancy; Growdon, John H.; Vieregge, Peter; Pramstaller, Peter P.; Klein, Christine; Hubble, Jean P.; Reider, Carson R.; Stacy, Mark; MacDonald, Marcy E.; Gusella, James F.; Myers, Richard H.

In: American Journal of Human Genetics, Vol. 70, No. 5, 01.01.2002, p. 1089-1095.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PARK3 influences age at onset in Parkinson disease

T2 - A genome scan in the GenePD study

AU - DeStefano, Anita L.

AU - Lew, Mark F.

AU - Golbe, Lawrence

AU - Mark, Margery

AU - Lazzarini, Alice M.

AU - Guttman, Mark

AU - Montgomery, Erwin

AU - Waters, Cheryl H.

AU - Singer, Carlos

AU - Watts, Ray L.

AU - Currie, Lillian J.

AU - Wooten, G. Frederick

AU - Maher, Nancy E.

AU - Wilk, Jemma B.

AU - Sullivan, Kristin M.

AU - Slater, Karen M.

AU - Saint-Hilaire, Marie H.

AU - Feldman, Robert G.

AU - Suchowersky, Oksana

AU - Lafontaine, Anne Louise

AU - Labelle, Nancy

AU - Growdon, John H.

AU - Vieregge, Peter

AU - Pramstaller, Peter P.

AU - Klein, Christine

AU - Hubble, Jean P.

AU - Reider, Carson R.

AU - Stacy, Mark

AU - MacDonald, Marcy E.

AU - Gusella, James F.

AU - Myers, Richard H.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: Chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P =. 02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.

AB - Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: Chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P =. 02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.

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