title: Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
abstract: Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
authors.affiliation: Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
authors.forename: Beth
authors.initials: B
authors.lastname: Knowlton
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: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Russel L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenblatt
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Catherine
authors.initials: C
authors.lastname: Dode
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelletto
authors.forename: Marina
authors.initials: M
authors.lastname: Frontali
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Trent
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McCusker
authors.forename: Estrella
authors.initials: E
authors.lastname: Gómez-Tortosa
authors.forename: David
authors.initials: D
authors.lastname: Mayo Cabrero
authors.forename: Randi
authors.initials: R
authors.lastname: Jones
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanko
authors.forename: Martha
authors.initials: M
authors.lastname: Nance
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Abramson
authors.forename: Oksana
authors.initials: O
authors.lastname: Suchowersky
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.forename: Madaline B
authors.initials: MB
authors.lastname: Harrison
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Mysore
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: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002894:Chromosomes, Human, Pair 4; D008040:Genetic Linkage; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D051957:MSX1 Transcription Factor; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D014157:Transcription Factors