Genome-wide association studies identify novel loci in rapidly progressive Alzheimer's disease

被引:0
作者
Wang, Ping [1 ,9 ]
Lynn, Audrey [1 ,2 ]
Miskimen, Kristy [1 ]
Song, Yeunjoo E. [1 ]
Wisniewski, Thomas [3 ]
Cohen, Mark [4 ,5 ]
Appleby, Brian S. [4 ,5 ,6 ,7 ]
Safar, Jiri G. [4 ,6 ,8 ]
Haines, Jonathan L. [1 ,2 ,10 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH USA
[2] Cleveland Inst Computat Biol, Cleveland, OH USA
[3] NYU, Ctr Cognit Neurol, Grossman Sch Med, Dept Neurol Pathol & Psychiat, New York, NY USA
[4] Case Western Reserve Univ, Dept Pathol, Cleveland, OH USA
[5] Case Western Reserve Univ, Natl Pr Dis Pathol Surveillance Ctr, Cleveland, OH USA
[6] Case Western Reserve Univ, Dept Neurol, Cleveland, OH USA
[7] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH USA
[8] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH USA
[9] Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, 1-326 Wolstein Res Bldg,2103 Cornell Rd, Cleveland, OH 44106 USA
[10] Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, 2-529 Wolstein Res Bldg,2103 Cornell Rd, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
Alzheimer's disease; genetic risk; rapid progression; APOLIPOPROTEIN-E; NATIONAL INSTITUTE; COGNITIVE DECLINE; BETA; METAANALYSIS; GUIDELINES; HISPANICS; GENOTYPE; INSIGHTS; FEATURES;
D O I
10.1002/alz.13655
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
INTRODUCTION: Recent data suggest that distinct prion-like amyloid beta and tau strains are associated with rapidly progressive Alzheimer's disease (rpAD). The role of genetic factors in rpAD is largely unknown.METHODS: Previously known AD risk loci were examined in rpAD cases. Genomewide association studies (GWAS) were performed to identify variants that influence rpAD. RESULTS: We identified 115 pathology-confirmed rpAD cases and 193 clinical rpAD cases, 80% and 69% were of non-Hispanic European ancestry. Compared to the clinical cohort, pathology-confirmed rpAD had higher frequencies of apolipoprotein E (APOE) epsilon 4 and rare missense variants in AD risk genes. A novel genome-wide significant locus (P < 5x10(-8)) was observed for clinical rpAD on chromosome 21 (rs2832546); 102 loci showed suggestive associations with pathology-confirmed rpAD (P < 1x10(-5)).DISCUSSION: rpAD constitutes an extreme subtype of AD with distinct features. GWAS found previously known and novel loci associated with rpAD.
引用
收藏
页码:2034 / 2046
页数:13
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