Journal article
Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease
American journal of medical genetics. Part A, Vol.119A(3), pp.279-282
06/15/2003
DOI: 10.1002/ajmg.a.20190
PMID: 12784292
Abstract
Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47–83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
Details
- Title: Subtitle
- Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease
- Creators
- L Djoussé - Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MassachusettsB Knowlton - Department of Neurology, Boston University School of Medicine, Boston, MassachusettsM Hayden - University of British Columbia, Center for Molecular Medicine & Therapeutics, Vancouver, British ColumbiaE.W Almqvist - University of British Columbia, Center for Molecular Medicine & Therapeutics, Vancouver, British ColumbiaR Brinkman - University of British Columbia, Center for Molecular Medicine & Therapeutics, Vancouver, British ColumbiaC Ross - John Hopkins University, Department of Neurology, Baltimore, MarylandR Margolis - John Hopkins University, Department of Neurology, Baltimore, MarylandA Rosenblatt - John Hopkins University, Department of Neurology, Baltimore, MarylandA Durr - Hôpital de la Salpetriere, Paris, FranceC Dode - Hôpital de la Salpetriere, Paris, FranceP.J Morrison - Department of Medical Genetics, Belfast City Hospital Trust, Belfast, United KingdomA Novelletto - Department of Cell Biology, University of Calabria, Rende, ItalyM Frontali - Institute of Experimental Medicine, CNR, Rome, ItalyR.J.A Trent - Department of Medicine, University of Sydney, Sydney, AustraliaE McCusker - Neurology Department, Westmead Hospital, Sydney, AustraliaE Gómez-Tortosa - Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid, SpainD Mayo - Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid, SpainR Jones - Emory Neurobehavioral Center, Atlanta, GeorgiaA Zanko - UCSF Division of Medical Genetics, San Francisco, CaliforniaM Nance - Hennepin County Medical Center, Department of Neurology, Minneapolis, MinnesotaR Abramson - Department of Neuropsychiatry & Behavior, WMS Hall Psychiatric Institute, Columbia, South CarolinaO Suchowersky - Department of Neurosciences, University Med. Clinic/Foothills, Calgary, AlbertaJ Paulsen - University of Iowa, Department of Psychiatry, Iowa City, IowaM Harrison - University of Virginia, Department of Neurology, Charlottesville, VirginiaQ Yang - Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, MassachusettsL.A Cupples - Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, MassachusettsJ.F Gusella - Department of Genetics, Harvard Medical School, Boston, MassachusettsM.E MacDonald - Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, MassachusettsR.H Myers - Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.119A(3), pp.279-282
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/ajmg.a.20190
- PMID
- 12784292
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Number of pages
- 4
- Grant note
- name: Huntington's Disease Center Without Walls (PHS Grant), award: P50NS016367; name: The Massachusetts Huntington's Disease Society of America; name: The Coalition for the Cure of HDSA; name: The Jerry and Hazel McDonald Huntington's Disease Research Fund
- Language
- English
- Date published
- 06/15/2003
- Academic Unit
- Psychiatry; Psychological and Brain Sciences
- Record Identifier
- 9984083845102771
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