Familial influence on age of onset among siblings with Huntington disease

• Published in: American journal of medical genetics 2001-07, Vol.105 (5), p.399-403
• Main Authors: Rosenblatt, Adam, Brinkman, R.R., Liang, K.Y., Almqvist, E.W., Margolis, R.L., Huang, C.Y., Sherr, M., Franz, M.L., Abbott, M.H., Hayden, M.R., Ross, C.A.
• Format: Article
• Language: English
• Subjects: Age of Onset; basal ganglia; Biological and medical sciences; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA - genetics; Family Health; Female; hereditary; Humans; Huntington Disease - genetics; Huntington Disease - pathology; Male; Medical sciences; neurodegenerative; Neurology; sibling pairs; Trinucleotide Repeats - genetics
• ISSN: 0148-7299; 1096-8628; 1096-8628
• DOI: 10.1002/ajmg.1400

In order to provide data relevant to a search for modifying genes for age of onset in Huntington disease, we examined the relationship between CAG number and age of onset in a total of 370 individuals from 165 siblingships, in two cohorts of siblings with Huntington disease: an American group of 144 individuals from 64 siblingships, and a Canadian population of 255 individuals from 113 siblingships. Using a logarithmic model to regress the age of onset on the number of CAG triplets, we found that CAG number alone accounted for 65%–71% of the variance in age of onset. The siblingship an individual belonged to accounted for 11%–19% of additional variance. This adds to the previous evidence that there are familial modifiers of the age of onset, independent of the CAG number. Such modifiers may consist of additional genes, which could be the target of a linkage study. A linkage study is feasible with the cooperation of a number of major centers and may be made more efficient by concentrating on sibling pairs that are highly discordant for age of onset. © 2001 Wiley‐Liss, Inc.