Age at onset in two common neurodegenerative diseases is genetically controlled.
To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%--60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases.
Li
Yi-Ju
YJ
Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
Scott
William K
WK
Hedges
Dale J
DJ
Zhang
Fengyu
F
Gaskell
P Craig
PC
Nance
Martha A
MA
Watts
Ray L
RL
Hubble
Jean P
JP
Koller
William C
WC
Pahwa
Rajesh
R
Stern
Matthew B
MB
Hiner
Bradley C
BC
Jankovic
Joseph
J
Allen
Fred A
FA
Goetz
Christopher G
CG
Mastaglia
Frank
F
Stajich
Jeffrey M
JM
Gibson
Rachel A
RA
Middleton
Lefkos T
LT
Saunders
Ann M
AM
Scott
Burton L
BL
Small
Gary W
GW
Nicodemus
Kristin K
KK
Reed
Allison D
AD
Schmechel
Donald E
DE
Welsh-Bohmer
Kathleen A
KA
Conneally
P Michael
PM
Roses
Allen D
AD
Gilbert
John R
JR
Vance
Jeffery M
JM
Haines
Jonathan L
JL
Pericak-Vance
Margaret A
MA
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D008957:Models, Genetic; D020412:Multifactorial Inheritance; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*
D001057:Apolipoproteins E