F1–01–01: Meta‐analysis in more than 74,000 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Abstract
Previous genome-wide association studies (GWAS) in individuals of European ancestry identified 9 other genomic regions associated with LOAD. However, the genetic component of AD is far away to be fully characterised. The search for additional common genetic risk factors requires large-scale meta-analysis of GWAS to increase the statistical power to identify the remaining genetic variations associated with AD risk which may primarily consist of variants with small effect or rare variants. To identify new LOAD genes, we conducted under the name of I-GAP (International Genomics of Alzheimer's Project), a large two-stage genome-wide association study (GWAS) on individuals of European ancestry. For stage 1, we meta-analysed four previously published GWAS datasets consisting of 17,008 AD cases and 37,646 controls using genotyped and imputed data (7,055,881 single nucleotide polymorphisms (SNPs)). For stage 2, 11,632 SNPs (p<10–3 in stage 1) were analysed in an independent set of 8,572 AD cases and 11,312 controls. In addition to the apolipoprotein E locus, we identified 19 loci reaching genome-wide significance level (P<5x10–8) in the combined discovery and replication data of which 11 were not identified in GWAS earlier. Of note, the results from the combined Stage 1 and Stage 2 datasets also indicated 13 suggestive loci of interest (P<10–6). In summary our GWAS meta-analysis for Alzheimer's disease has identified eleven new susceptibility loci in or near plausible candidate in ad…
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Inpp5d is genetically associated with Alzheimer's disease risk.
“Inpp5d is genetically associated with Alzheimer's disease risk.”
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Genetic studies have identified numerous AD risk variants in immune- and microglial-associated genes.
“Genetic studies have identified numerous AD risk variants in immune‐ and microglial‐associated genes, highlighting the importance of microglia function in disease progression. 3 , 4 , 5 , 6 , 7”
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HLA-DRB polymorphisms are associated with increased risk of AD.
“Moreover, HLA‐DRB polymorphisms are associated with increased risk of AD 2 , 19 , 20”
From The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model (2022) · cites this paper as [20]
The APOE gene is an impressive genome-wide association signal for risk of Alzheimer's disease.
“In genome‐wide association studies (GWASs) the apolipoprotein E (APOE) gene stands out as an impressive signal for risk of Alzheimer's disease (AD), 6 , 7”
From <i>APOE</i> and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [6]
APOE ε4 is the main contributor to late-onset AD and has provided the clearest and most consistent signal in GWASs.
“Whereas APOE ε4 is the main contributor to late‐onset AD, and has provided the clearest and most consistent signal in GWASs, 6 , 7”
From <i>APOE</i> and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [6]
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- Authors
- Lambert, J.
- Affiliations
- Inserm (FR)
- Corresponding author
- Lambert, Jean‐Charles
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2013-07
- Volume
- 9
- Issue
- 4S_Part_3
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2036722142
- Cited by
- 32
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2019: 9 · 2018: 2 · 2017: 3 · 2015: 3 · 2014: 2 · 2013: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, late-onset Alzheimer's disease
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