4.8 Article

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Journal

NATURE GENETICS
Volume 45, Issue 12, Pages 1452-U206

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2802

Keywords

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Funding

  1. French National Foundation on Alzheimer's Disease and Related Disorders
  2. Institut Pasteur de Lille
  3. INSERM
  4. FRC (Fondation pour la Recherche sur le Cerveau)
  5. Rotary
  6. LABEX (Laboratory of Excellence Program Investment for the Future)
  7. DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease)
  8. Alzheimer's Association (Chicago, Illinois)
  9. Wellcome Trust
  10. MRC
  11. Alzheimer's Research UK (ARUK)
  12. Welsh government
  13. US National Institutes of Health, National Institute on Aging (NIH-NIA) [U01 AG032984, R01 AG033193]
  14. US National Institutes of Health
  15. Erasmus Medical Center
  16. Erasmus University
  17. Alzheimers Research UK [ART-RF2007-3, ARUK-PG2014-1, ARUK-NCG2012B-1, ART-BIG2009-1, ART-PhD2011-10] Funding Source: researchfish
  18. Alzheimer's Society [164] Funding Source: researchfish
  19. Medical Research Council [MC_U137686857, MC_U123160657, G0801306, MC_G1000734, MR/K013041/1, G0601846, MC_U123160651, MC_U105292687, MC_PC_14095, G0902227] Funding Source: researchfish
  20. National Institute for Health Research [NF-SI-0611-10084, NF-SI-0508-10123] Funding Source: researchfish
  21. MRC [G0902227, MC_U105292687, MC_PC_14095, MC_G1000734, MC_U123160651, G0801306, MC_U137686857, MR/K013041/1, G0601846, MC_U123160657] Funding Source: UKRI

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Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

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