TY - JOUR
T1 - A genome scan for modifiers of age at onset in Huntington disease
T2 - The HD MAPS study
AU - Li, Jian Liang
AU - Hayden, Michael R.
AU - Almqvist, Elisabeth W.
AU - Brinkman, Ryan R.
AU - Durr, Alexandra
AU - Dodé, Catherine
AU - Morrison, Patrick J.
AU - Suchowersky, Oksana
AU - Ross, Christopher A.
AU - Margolis, Russell L.
AU - Rosenblatt, Adam
AU - Gómez-Tortosa, Estrella
AU - Cabrero, David Mayo
AU - Novelletto, Andrea
AU - Frontali, Marina
AU - Nance, Martha
AU - Trent, Ronald J.A.
AU - McCusker, Elizabeth
AU - Jones, Randi
AU - Paulsen, Jane S.
AU - Harrison, Madeline
AU - Zanko, Andrea
AU - Abramson, Ruth K.
AU - Russ, Ana L.
AU - Knowlton, Beth
AU - Djoussé, Luc
AU - Mysore, Jayalakshmi S.
AU - Tariot, Suzanne
AU - Gusella, Michael F.
AU - Wheeler, Vanessa C.
AU - Atwood, Larry D.
AU - Cupples, L. Adrienne
AU - Saint-Hilaire, Marie
AU - Cha, Jang Ho J.
AU - Hersch, Steven M.
AU - Koroshetz, Walter J.
AU - Gusella, James F.
AU - MacDonald, Marcy E.
AU - Myers, Richard H.
N1 - Funding Information:
This study was supported by Public Health Service Grant P50NS016367 (Huntington’s Disease Center without Walls) and by grants from the Massachusetts Huntington’s Disease Society of America, the HDSA Coalition for the Cure, the Jerry McDonald Huntington’s Disease Research Fund, and the Canadian Institute of Health Research.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
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U2 - 10.1086/378133
DO - 10.1086/378133
M3 - Article
C2 - 12900792
AN - SCOPUS:0041385579
SN - 0002-9297
VL - 73
SP - 682
EP - 687
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -