title: PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study.
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.
authors.affiliation: Department of Neurology, Boston University Schools of Medicine and of Public Health, Boston, MA 02118, USA. adestef@bu.edu
authors.forename: Anita L
authors.initials: AL
authors.lastname: DeStefano
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lew
authors.forename: Lawrence I
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authors.lastname: Golbe
authors.forename: Margery H
authors.initials: MH
authors.lastname: Mark
authors.forename: Alice M
authors.initials: AM
authors.lastname: Lazzarini
authors.forename: Mark
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authors.lastname: Guttman
authors.forename: Erwin
authors.initials: E
authors.lastname: Montgomery
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Waters
authors.forename: Carlos
authors.initials: C
authors.lastname: Singer
authors.forename: Ray L
authors.initials: RL
authors.lastname: Watts
authors.forename: Lillian J
authors.initials: LJ
authors.lastname: Currie
authors.forename: G Frederick
authors.initials: GF
authors.lastname: Wooten
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Maher
authors.forename: Jemma B
authors.initials: JB
authors.lastname: Wilk
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Karen M
authors.initials: KM
authors.lastname: Slater
authors.forename: Marie H
authors.initials: MH
authors.lastname: Saint-Hilaire
authors.forename: Robert G
authors.initials: RG
authors.lastname: Feldman
authors.forename: Oksana
authors.initials: O
authors.lastname: Suchowersky
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Lafontaine
authors.forename: Nancy
authors.initials: N
authors.lastname: Labelle
authors.forename: John H
authors.initials: JH
authors.lastname: Growdon
authors.forename: Peter
authors.initials: P
authors.lastname: Vieregge
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Jean P
authors.initials: JP
authors.lastname: Hubble
authors.forename: Carson R
authors.initials: CR
authors.lastname: Reider
authors.forename: Mark
authors.initials: M
authors.lastname: Stacy
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008875:Middle Aged; D009679:Nuclear Family; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*