Age at onset in two common neurodegenerative diseases is genetically controlled

被引:240
作者
Li, YJ
Scott, WK
Hedges, DJ
Zhang, FY
Gaskell, PC
Nance, MA
Watts, RL
Hubble, JP
Koller, WC
Pahwa, R
Stern, MB
Hiner, BC
Jankovic, J
Allen, AA
Goetz, CG
Mastaglia, F
Stajich, JM
Gibson, RA
Middleton, LT
Saunders, AM
Scott, BL
Small, GW
Nicodemus, KK
Reed, AD
Schmechel, DE
Welsh-Bohmer, KA
Conneally, PM
Roses, AD
Gilbert, JR
Vance, JM
Haines, JL
Pericak-Vance, MA
机构
[1] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA
[4] Struthers Parkinson Ctr, Golden Valley, MN USA
[5] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
[6] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA
[7] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA
[8] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA
[9] Univ Penn Hlth Syst, Dept Neurol, Philadelphia, PA USA
[10] Marshfield Clin Fdn Med Res & Educ, Dept Neurol, Marshfield, WI USA
[11] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA
[12] Carolina Neurol Clin, Charlotte, NC USA
[13] Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA
[14] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Perth, WA 6009, Australia
[15] GlaxoSmithKline Res & Dev Ltd, Greenford, Middx, England
[16] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA
[17] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA
[18] Vanderbilt Univ, Med Ctr, Program Human Genet, Nashville, TN USA
[19] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA
[20] GlaxoSmithKline, Genet Res Directorate, Res Triangle Pk, NC USA
关键词
D O I
10.1086/339815
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n = 449) and Parkinson disease (PD; n = 174). Heritabilities between 40%- 60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases.
引用
收藏
页码:985 / 993
页数:9
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