DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Cerebrospinal AB1-42 levels in Alzheimer's disease dementia. The EFO term beta-amyloid 1-42 measurement, Alzheimers disease was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: beta-amyloid 1-42 measurement, Alzheimers disease

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

A Ramirez, WM van der Flier, C Herold, D Ramonet, S Heilmann, P Lewczuk, J Popp, A Lacour, D Drichel, E Louwersheimer, MP Kummer, C Cruchaga, P Hoffmann, C Teunissen, H Holstege, J Kornhuber, O Peters, AC Naj, V Chouraki, C Bellenguez, A Gerrish, R Heun, L Frölich, M Hüll, L Buscemi, S Herms, H Kölsch, P Scheltens, MM Breteler, E Rüther, J Wiltfang, A Goate, F Jessen, W Maier, MT Heneka, T Becker, MM Nöthen

TITLE:

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

JOURNAL:

Human molecular genetics Dec 2014, Vol 23, pp. 6644-58

ABSTRACT:

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42. PUBMED: 25027320
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