Impact of Parkinson's disease risk loci on age at onset

被引：40
|
作者：
Lill, Christina M. [1 ,2 ]
Hansen, Johnni [3 ,4 ]
Olsen, Jorgen H. [3 ]
Binder, Harald [5 ]
Ritz, Beate [4 ]
Bertram, Lars [1 ,2 ,6 ]
机构：
[1] Med Univ Lubeck, Platform Genome Analyt, Inst Neurogenet, D-23562 Lubeck, Germany
[2] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany
[3] Danish Canc Soc, Res Ctr, Inst Canc Epidemiol, Copenhagen, Denmark
[4] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol & Environm Sci, Los Angeles, CA 90024 USA
[5] Univ Med Ctr Mainz, Inst Med Biostat Epidemiol & Informat IMBEI, Mainz, Germany
[6] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, London, England
来源：
MOVEMENT DISORDERS | 2015年 / 30卷 / 06期
基金：
美国国家卫生研究院;
关键词：
Parkinson's disease; PD; age at onset; genetic association; genome-wide association study; GWAS; genetic risk score; GAK; DGKQ; GBA; N370S;
D O I：
10.1002/mds.26237
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
BackgroundThe aim of this study was to assess whether recently identified Parkinson's disease (PD) risk genes also influence age at onset in PD. MethodsWe genotyped 23 single-nucleotide polymorphisms in 1,526 Danish PD patients and performed linear regression analyses with age at onset. The combined impact of PD risk loci on age at onset was assessed by linear regression analyses using a weighted genetic risk score. ResultsThe strongest effects were observed with rs12726330 in GBA (beta=-3.63, P = 2.0 x 10(-5)) and rs34311866 in TMEM175/GAK (beta=-1.19, P = 4.0 x 10(-3)), corresponding to a 3.6-y and 1.2-y decrease of age at onset per risk allele, respectively. The weighted genetic risk score yielded significant association with reduced onset age (P = 3.98 x 10(-3)), although the variance explained was small (0.6%), and the effect was mostly driven by polymorphisms in GBA and TMEM175/GAK. ConclusionsOverall, our study indicates that GBA and TMEM175/GAK significantly alter age at onset in PD. (c) 2015 International Parkinson and Movement Disorder Society
引用
收藏
页码：847 / 850
页数：4
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