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


METHODS
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.


METHODS
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.
Scott
W K
WK
Center for Human Genetics, Box 3445, Duke University Medical Center, Durham, NC 27710, USA.
Nance
M A
MA
Watts
R L
RL
Hubble
J P
JP
Koller
W C
WC
Lyons
K
K
Pahwa
R
R
Stern
M B
MB
Colcher
A
A
Hiner
B C
BC
Jankovic
J
J
Ondo
W G
WG
Allen
F H
FH
Goetz
C G
CG
Small
G W
GW
Masterman
D
D
Mastaglia
F
F
Laing
N G
NG
Stajich
J M
JM
Slotterbeck
B
B
Booze
M W
MW
Ribble
R C
RC
Rampersaud
E
E
West
S G
SG
Gibson
R A
RA
Middleton
L T
LT
Roses
A D
AD
Haines
J L
JL
Scott
B L
BL
Vance
J M
JM
Pericak-Vance
M A
MA
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D004351:Drug Resistance; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008025:Ligases / Q000235:genetics; D008126:Lod Score; D018895:Microsatellite Repeats; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases
D000978:Antiparkinson Agents; D007980:Levodopa; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases