PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study.
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.
DeStefano
Anita L
AL
Department of Neurology, Boston University Schools of Medicine and of Public Health, Boston, MA 02118, USA. adestef@bu.edu
Lew
Mark F
MF
Golbe
Lawrence I
LI
Mark
Margery H
MH
Lazzarini
Alice M
AM
Guttman
Mark
M
Montgomery
Erwin
E
Waters
Cheryl H
CH
Singer
Carlos
C
Watts
Ray L
RL
Currie
Lillian J
LJ
Wooten
G Frederick
GF
Maher
Nancy E
NE
Wilk
Jemma B
JB
Sullivan
Kristin M
KM
Slater
Karen M
KM
Saint-Hilaire
Marie H
MH
Feldman
Robert G
RG
Suchowersky
Oksana
O
Lafontaine
Anne-Louise
AL
Labelle
Nancy
N
Growdon
John H
JH
Vieregge
Peter
P
Pramstaller
Peter P
PP
Klein
Christine
C
Hubble
Jean P
JP
Reider
Carson R
CR
Stacy
Mark
M
MacDonald
Marcy E
ME
Gusella
James F
JF
Myers
Richard H
RH
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*