A genome scan for modifiers of age at onset in Huntington disease:: The HD MAPS study

被引：106

作者：

Li, JL

Hayden, MR

Almqvist, EW

Brinkman, RR

Durr, A

Dodé, C

Morrison, PJ

Suchowersky, O

Ross, CA

Margolis, RL

Rosenblatt, A

Gómez-Tortosa, E

Cabrero, DM

Novelletto, A

Frontali, M

Nance, M

Trent, RJA

McCusker, E

Jones, R

Paulsen, JS

Harrison, M

Zanko, A

Abramson, RK

Russ, AL

Knowlton, B

Djoussé, L

Mysore, JS

Tariot, S

Gusella, MF

Wheeler, VC

Atwood, LD

Cupples, LA

Saint-Hilaire, M

Cha, JHJ

Hersch, SM

Koroshetz, WJ

Gusella, JF

MacDonald, ME

Myers, RH

机构：

[1] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[2] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Evans Dept Med, Boston, MA 02118 USA

[3] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[4] Boston Univ, Sch Publ Hlth, Bioinformat Program, Boston, MA USA

[5] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[6] Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA

[7] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[8] Wyeth Res, Dept Genom, Cambridge, MA USA

[9] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada

[10] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada

[11] Hop La Pitie Salpetriere, INSERM, U289, Paris, France

[12] Hop Cochin, Serv Biochim & Genet Mol, F-75674 Paris, France

[13] Belfast City Hosp, Dept Med Genet, Belfast BT9 7AD, Antrim, North Ireland

[14] Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland

[15] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada

[16] Univ Calgary, Dept Med Genet, Calgary, AB, Canada

[17] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA

[18] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA

[19] Johns Hopkins Univ, Program Cellular & Mol Med, Baltimore, MD USA

[20] Fdn Jimenez Diaz, Serv Neurol & Genet, E-28040 Madrid, Spain

[21] Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Italy

[22] CNR, Inst Neurobiol & Mol Med, Rome, Italy

[23] Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA

[24] Univ Sydney, Dept Med, Sydney, NSW 2006, Australia

[25] Westmead Hosp, Dept Neurol, Sydney, NSW, Australia

[26] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA

[27] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA

[28] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA

[29] Univ Calif San Francisco, Div Med Genet, San Francisco, CA 94143 USA

[30] William S Hall Psychiat Inst, Columbia, SC USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2003年 / 73卷 / 03期

关键词：

D O I：

10.1086/378133

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 (h(2) = 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.

引用

页码：682 / 687

页数：6

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