title: Parkinson disease loci in the mid-western Amish.
abstract: Previous evidence has shown that Parkinson disease (PD) has a heritable component, but only a small proportion of the total genetic contribution to PD has been identified. Genetic heterogeneity complicates the verification of proposed PD genes and the identification of new PD susceptibility genes. Our approach to overcome the problem of heterogeneity is to study a population isolate, the mid-western Amish communities of Indiana and Ohio. We performed genome-wide association and linkage analyses on 798 individuals (31 with PD), who are part of a 4,998 member pedigree. Through these analyses, we identified a region on chromosome 5q31.3 that shows evidence of association (p value < 1 × 10(-4)) and linkage (multipoint HLOD = 3.77). We also found further evidence of linkage on chromosomes 6 and 10 (multipoint HLOD 4.02 and 4.35 respectively). These data suggest that locus heterogeneity, even within the Amish, may be more extensive than previously appreciated.
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Davis
authors.forename: A C
authors.initials: AC
authors.lastname: Cummings
authors.forename: L N
authors.initials: LN
authors.lastname: D'Aoust
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.forename: D R
authors.initials: DR
authors.lastname: Velez Edwards
authors.forename: R
authors.initials: R
authors.lastname: Laux
authors.forename: L
authors.initials: L
authors.lastname: Reinhart-Mercer
authors.forename: D
authors.initials: D
authors.lastname: Fuzzell
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: S L
authors.initials: SL
authors.lastname: Lee
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D061365:Amish / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D019295:Computational Biology; D008040:Genetic Linkage; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007196:Indiana; D009820:Ohio; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide