Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2.
Late-onset familial Alzheimer disease (LOFAD) is a genetically heterogeneous and complex disease for which only one locus, APOE, has been definitively identified. Difficulties in identifying additional loci are likely to stem from inadequate linkage analysis methods. Nonparametric methods suffer from low power because of limited use of the data, and traditional parametric methods suffer from limitations in the complexity of the genetic model that can be feasibly used in analysis. Alternative methods that have recently been developed include Bayesian Markov chain-Monte Carlo methods. These methods allow multipoint linkage analysis under oligogenic trait models in pedigrees of arbitrary size; at the same time, they allow for inclusion of covariates in the analysis. We applied this approach to an analysis of LOFAD on five chromosomes with previous reports of linkage. We identified strong evidence of a second LOFAD gene on chromosome 19p13.2, which is distinct from APOE on 19q. We also obtained weak evidence of linkage to chromosome 10 at the same location as a previous report of linkage but found no evidence for linkage of LOFAD age-at-onset loci to chromosomes 9, 12, or 21.
Wijsman
Ellen M
EM
Division of Medical Genetics, Department of Medicine, University of Washington,Seattle, WA 98195-7720, USA. wijsman@u.washington.edu
Daw
E Warwick
EW
Yu
Change-En
CE
Payami
Haydeh
H
Steinbart
Ellen J
EJ
Nochlin
David
D
Conlon
Erin M
EM
Bird
Thomas D
TD
Schellenberg
Gerard D
GD
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001499:Bayes Theorem; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000648:ultrastructure; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19 / Q000648:ultrastructure*; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure; D005192:Family Health; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009010:Monte Carlo Method; D040641:Quantitative Trait Loci
D005819:Genetic Markers