Document Detail


Indexing disease progression at study entry with individuals at-risk for Huntington disease.
MedLine Citation:
PMID:  21858921     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The identification of clinical and biological markers of disease in persons at risk for Huntington disease (HD) has increased in efforts to better quantify and characterize the epoch of prodrome prior to clinical diagnosis. Such efforts are critical in the design and implementation of clinical trials for HD so that interventions can occur at a time most likely to increase neuronal survival and maximize daily functioning. A prime consideration in the examination of prodromal individuals is their proximity to diagnosis. It is necessary to quantify proximity so that individual differences in key marker variables can be properly interpreted. We take a data-driven approach to develop an index that can be viewed as a proxy for time to HD diagnosis known as the CAG-Age Product Scaled or CAP(S) . CAP(S) is an observed utility variable computed for all genetically at-risk individuals based on age at study entry and CAG repeat length. Results of a longitudinal receiver operating characteristic (ROC) analysis showed that CAP(S) had a relatively strong ability to predict individuals who became diagnosed, especially in the first 2 years. Bootstrap validation provided evidence that CAP(S) computed on a new sample from the same population could have similar discriminatory power. Cutoffs for the empirical CAP(S) distribution can be used to create a classification for mutation-positive individuals (Low-Med-High), which is, useful for comparison with the naturally occurring mutation-negative Control group. The classification is an improvement over the one currently in use as it is based on observed data rather than model-based estimated values. © 2011 Wiley-Liss, Inc.
Authors:
Ying Zhang; Jeffrey D Long; James A Mills; John H Warner; Wenjing Lu; Jane S Paulsen;
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-19
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  156B     ISSN:  1552-485X     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-09-07     Completed Date:  2012-01-17     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  751-63     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
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MeSH Terms
Descriptor/Qualifier:
Aging / pathology
Area Under Curve
Confidence Intervals
Disease Progression*
Humans
Huntington Disease / classification,  genetics,  pathology*
Models, Statistical
Reproducibility of Results
Risk Factors
Trinucleotide Repeat Expansion / genetics
Grant Support
ID/Acronym/Agency:
NS40068/NS/NINDS NIH HHS; R01 NS040068/NS/NINDS NIH HHS; R01 NS040068-11/NS/NINDS NIH HHS
Comments/Corrections

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