Journal article
CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.153B(2), pp.397-408
03/05/2010
DOI: 10.1002/ajmg.b.30992
PMCID: PMC3048807
PMID: 19548255
Abstract
CAG-repeat length in the gene for HD is inversely correlated with age of onset (AOO). A number of statistical models elucidating the relationship between CAG length and AOO have recently been published. In the present article, we review the published formulae, summarize essential differences in participant sources, statistical methodologies, and predictive results. We argue that unrepresentative sampling and failure to use appropriate survival analysis methodology may have substantially biased much of the literature. We also explain why the survival analysis perspective is necessary if any such model is to undergo prospective validation. We use prospective diagnostic data from the PREDICT-HD longitudinal study of CAG-expanded participants to test conditional predictions derived from two survival models of AOO of HD. A prior model of the relationship of CAG and AOO originally published by Langbehn et al. yields reasonably accurate predictions, while a similar model by Gutierrez and MacDonald substantially overestimates diagnosis risk for all but the highest risk participants in this sample. The Langbehn et al. model appears accurate enough to have substantial utility in various research contexts. We also emphasize remaining caveats, many of which are relevant for any direct application to genetic counseling.
Details
- Title: Subtitle
- CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches
- Creators
- Douglas R Langbehn - Department of Biostatistics, School of Public Health, University of Iowa, Iowa City, IowaMichael R Hayden - Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, CanadaJane S Paulsen - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IAPREDICT-HD Investigators of the Huntington Study Group
- Contributors
- Hans J Johnson (Contributor) - University of Iowa, Electrical and Computer Engineering
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.153B(2), pp.397-408
- DOI
- 10.1002/ajmg.b.30992
- PMID
- 19548255
- PMCID
- PMC3048807
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Publisher
- United States
- Grant note
- R01 NS040068 / NINDS NIH HHS R01 NS040068-10 / NINDS NIH HHS UL1 TR000040 / NCATS NIH HHS UL1 TR000442 / NCATS NIH HHS S10 RR023392 / NCRR NIH HHS 5R01NS40068-09 / NINDS NIH HHS
- Language
- English
- Date published
- 03/05/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; The Iowa Institute for Biomedical Imaging; The Iowa Initiative for Artificial Intelligence; Iowa Informatics Initiative
- Record Identifier
- 9984003918502771
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