title: A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study.
abstract: Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
authors.affiliation: Department of Neurology, Boston University School of Medicine, and Bioinformatics Program, School of Public Health, Boston University, Boston, MA, USA.
authors.forename: Jian-Liang
authors.initials: JL
authors.lastname: Li
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Elisabeth W
authors.initials: EW
authors.lastname: Almqvist
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodé
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Oksana
authors.initials: O
authors.lastname: Suchowersky
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenblatt
authors.forename: Estrella
authors.initials: E
authors.lastname: Gómez-Tortosa
authors.forename: David Mayo
authors.initials: DM
authors.lastname: Cabrero
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelletto
authors.forename: Marina
authors.initials: M
authors.lastname: Frontali
authors.forename: Martha
authors.initials: M
authors.lastname: Nance
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Trent
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McCusker
authors.forename: Randi
authors.initials: R
authors.lastname: Jones
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.forename: Madeline
authors.initials: M
authors.lastname: Harrison
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanko
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Abramson
authors.forename: Ana L
authors.initials: AL
authors.lastname: Russ
authors.forename: Beth
authors.initials: B
authors.lastname: Knowlton
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
authors.forename: Jayalakshmi S
authors.initials: JS
authors.lastname: Mysore
authors.forename: Suzanne
authors.initials: S
authors.lastname: Tariot
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gusella
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Wheeler
authors.forename: Larry D
authors.initials: LD
authors.lastname: Atwood
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Marie
authors.initials: M
authors.lastname: Saint-Hilaire
authors.forename: Jang-Ho J
authors.initials: JH
authors.lastname: Cha
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hersch
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koroshetz
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
mesh_terms: D017668:Age of Onset; D002874:Chromosome Mapping; D016678:Genome; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D018911:Trinucleotide Repeats