Journal article
A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study
American journal of human genetics, Vol.73(3), pp.682-687
09/2003
DOI: 10.1086/378133
PMCID: PMC1180695
PMID: 12900792
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.
Details
- Title: Subtitle
- A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study
- Creators
- Jian-Liang Li - Harvard Medical SchoolJane S Paulsen - Department of Neurology andMichael R Hayden - Department of Neurology andElisabeth W Almqvist - Department of Neurology andRyan R Brinkman - Department of Neurology andAlexandra Durr - Department of Neurology andCatherine Dodé - Department of Neurology andPatrick J Morrison - Department of Neurology andOksana Suchowersky - Department of Neurology andChristopher A Ross - Department of Neurology andRussell L Margolis - Department of Neurology andAdam Rosenblatt - Department of Neurology andEstrella Gómez-Tortosa - Department of Neurology andDavid Mayo Cabrero - Department of Neurology andAndrea Novelletto - Department of Neurology andMarina Frontali - Department of Neurology andMartha Nance - Department of Neurology andRonald J. A Trent - Department of Neurology andElizabeth McCusker - Department of Neurology andRandi Jones - Department of Neurology andMadeline Harrison - Department of Neurology andAndrea Zanko - Department of Neurology andRuth K Abramson - Department of Neurology andAna L Russ - Department of Neurology andBeth Knowlton - Department of Neurology andLuc Djoussé - Department of Neurology andJayalakshmi S Mysore - Department of Neurology andSuzanne Tariot - Department of Neurology andMichael F Gusella - Department of Neurology andVanessa C Wheeler - Department of Neurology andLarry D Atwood - Department of Neurology andL. Adrienne Cupples - Department of Neurology andMarie Saint-Hilaire - Department of Neurology andJang-Ho J Cha - Department of Neurology andSteven M Hersch - Department of Neurology andWalter J Koroshetz - Department of Neurology andJames F Gusella - Department of Neurology andMarcy E MacDonald - Department of Neurology andRichard H Myers - Department of Neurology and
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.73(3), pp.682-687
- Publisher
- The American Society of Human Genetics
- DOI
- 10.1086/378133
- PMID
- 12900792
- PMCID
- PMC1180695
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Alternative title
- Genome Scan for Onset Age Modifiers in HD
- Language
- English
- Date published
- 09/2003
- Academic Unit
- Psychiatry; Psychological and Brain Sciences
- Record Identifier
- 9984083997602771
Metrics
28 Record Views