Common variants in ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease
By P. Hollingworth, D. Harold, R. Sims, A. Gerrish, J. Lambert, M. Carrasquillo, R. Abraham, M. Hamshere, J. S. Pahwa, V. Moskvina and 162 more. Nature Genetics, 2011
1,932 citations recorded by the source corpus.
We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).
Subfields: Oncology, Physiology, Surgery
View Paper: https://www.semanticscholar.org/paper/d7984bd4d09f091b06dcba03d08de0d4c56ce33f
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Citations in the corpus
- Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease (2014, methodology): “Figure S4 QQ-plot of gene-wide p-values for all genes (A) and excluding previously reported[4-8] GWAS significantly associated genes ±0.”
- Epidemiology of Alzheimer Disease (2012, neutral): “The NIA-LOAD Family Study also replicated the variants in BIN1 and provided modest confirmation for CLU, but not for CR1 or PICALM after APOE adjustment (Hollingworth et al. 2011; Naj et al. 2011).”
- The genetics of Alzheimer disease. (2012, background): “1 10% Clearance of Ab; innate immunity CR1 Complement component (3b/4b) receptor 1 1q32 15% Clearance of Ab; innate immunity PICALM Phosphatidylinositol binding clathrin assembly molecule 11q14 15% Production and clearance of Ab; cellular signaling BIN1 Bridging integrator 1 2q14 15% Production and ”
- The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data (2014, neutral): “Additional AD risk variants were rapidly discovered as GWAS expanded to more populations with dementia and healthy controls (Hollingworth et al. 2011).”
- Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. (2015, background): “Recently, microglia became more important than ever before in demonstrating strong genetic implications for microglia molecules and the immune system, especially when genomewide association study (GWAS) have identified variants of several immune genes are risk factors for late onset Alzheimer’s dise”
- Neuroinflammation in Alzheimer's disease: Current evidence and future directions (2016, background): “Additionally, several other loci have been demonstrated including BIN1, EPHA1, MS4A, CD33, CD2AP, and ABCA7 [39].”
- Alzheimer's disease (2018, background): “A number of AD-risk genes, including CR1, CD33 and TREM2, are involved in immune system pathways [36,37].”
- Upregulated function of mitochondria-associated ER membranes in Alzheimer disease (2012, neutral): “Finally, our findings have implications for understanding the genetics of AD (Hollingworth et al , 2011; Naj et al , 2011).”