Study 5 of 8IGF-1 DES (Des(1-3) IGF-1) literatureeuropepmc · Meta-analysis

Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias.

This study identified 91 genetic loci associated with Alzheimer's disease risk, including 16 new loci, but further validation is needed to confirm their clinical relevance.

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Where it sits

this study against the rest of the igf-1 des (des(1-3) igf-1) corpus

Preclinical

Observational

Open-label

Randomised

Reviews · this one

Summary and findings

This meta-analysis examined the genetic architecture of Alzheimer's disease (AD) and related dementias (ADRD) in a population of 128,681 cases and 849,833 controls. It identified 91 genetic loci associated with ADRD risk, including 16 new loci, and reported a polygenic score linked to increased risk of AD pathology. No therapeutic claims are made.

How much of this paper we could read: full text read (0.90). We had a clear abstract, so the summary below closely tracks the paper. What this means →

Twofold increased risk of presenting with Braak neurofibrillary tangles stage of >4 in the tenth decile of the polygenic score compared to median score group.

Abstract

The authors’ words, as europepmc supplied them

To better characterize the genetic architecture underlying Alzheimer's disease (AD) and related dementias (ADRD), we performed a meta-analysis of European-ancestry genome-wide association studies in 128,681 cases or proxy cases of ADRD and 849,833 (proxy) controls. We identified 91 genetic loci associated with ADRD risk, of which 16 are new and 56 are specifically detected in clinically diagnosed AD cases. We also provide a list of 18 loci (15 new) requiring further external validation. A polygenic score combining the effects of ADRD loci other than APOE was primarily associated with AD rather than non-AD pathology. Individuals in the tenth decile of the score exhibited a twofold increased risk of presenting with Braak neurofibrillary tangles stage of >4 and moderate-to-severe neuritic amyloid plaque pathology at death compared to individuals in the median score group. In conclusion, our study validated a large number of loci associated with the risk of clinically diagnosed AD, while further investigations are required to confirm the impact of the other loci on AD clinical diagnosis and of each locus on AD pathology.

Background

Not reported in abstract.

Methods

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Results

Not reported in abstract.

Interpretation

Not reported in abstract.

Key findings

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Limitations

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Elsewhere in the IGF-1 DES (Des(1-3) IGF-1) corpus

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