A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

被引：841

作者：

Chang, Diana ^{[1
]}

Nalls, Mike A. ^{[2
,3
]}

Hallgrimsdottir, Ingileif B. ^{[4
,5
]}

Hunkapiller, Julie ^{[1
]}

van der Brug, Marcel ^{[1
,6
]}

Cai, Fang ^{[1
]}

Kerchner, Geoffrey A. ^{[1
]}

Ayalon, Gai ^{[1
]}

Bingol, Baris ^{[1
]}

Sheng, Morgan ^{[1
]}

Hinds, David ^{[4
]}

Behrens, Timothy W. ^{[1
]}

Singleton, Andrew B. ^{[2
]}

Bhangale, Tushar R. ^{[1
]}

Graham, Robert R. ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

[2] NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA

[3] Data Tecn Int, Glen Echo, MD USA

[4] 23&Me Inc, Mountain View, CA USA

[5] Amgen Inc, San Francisco, CA USA

[6] E Scape Bio, San Francisco, CA USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 10期

关键词：

IMPUTATION; GENETICS; DATABASE; VARIANTS; TRANSCRIPTOME; HERITABILITY; ALZHEIMERS; CATHEPSINS; IMMUNITY; PROGRESS;

D O I：

10.1038/ng.3955

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Common variant genome-wide association studies (GWASs) have, to date, identified > 24 risk loci for Parkinson's disease (PD). To discover additional loci, we carried out a GWAS comparing 6,476 PD cases with 302,042 controls, followed by a meta-analysis with a recent study of over 13,000 PD cases and 95,000 controls at 9,830 overlapping variants. We then tested 35 loci (P < 1 x 10(-6)) in a replication cohort of 5,851 cases and 5,866 controls. We identified 17 novel risk loci (P < 5 x 10(-8)) in a joint analysis of 26,035 cases and 403,190 controls. We used a neurocentric strategy to assign candidate risk genes to the loci. We identified protein-altering or cis-expression quantitative trait locus (cis-eQTL) variants in linkage disequilibrium with the index variant in 29 of the 41 PD loci. These results indicate a key role for autophagy and lysosomal biology in PD risk, and suggest potential new drug targets for PD.

引用

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页码：1511 / +

页数：8

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