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Genomic variation in educational attainment modifies Alzheimer disease risk
Open accessPublished version of a preprint
Abstract
Objective To determine the putative protective relationship of educational attainment on Alzheimer’s disease (AD) risk using Mendelian randomization, and to test the hypothesis that by using genetic regions surrounding individually associated SNPs as the instrumental variable we can identify genes that contribute to the relationship. Methods We performed Mendelian randomization using genome-wide association study summary statistics from studies of educational attainment and AD in two stages. Our instrumental variable comprised of i) 1,271 SNPs significantly associated with educational attainment and ii) individual 2Mb regions surrounding the genome-wide significant SNPs. Results A causal inverse relationship between educational attainment and AD was identified by the 1,271 SNPs (odds ratio = 0.63; 95% CI, 0.54-0.74; p =4.08×10 −8 ). Analysis of individual loci identified six regions that significantly replicated the causal relationship. Genes within these regions included LRRC2 , SSBP2 , and NEGR1 ; the latter a regulator of neuronal growth. Conclusions Educational attainment is an important protective factor for AD. Genomic regions that significantly paralleled the overall causal relationship contain genes expressed in neurons or involved in the regulation of neuronal development.
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“As previous studies and our results suggest, EduYears shows phenotypic correlations and shares genetic components with multiple traits and diseases relevant to medical research, including cognitive function, neurodegeneration and psychiatric disorders43–46”
From Shared genetic architectures of educational attainment in East Asian and European populations (2024) · cites this paper as [45]
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Flores-Dorantes, M. T., Díaz‐López, Y. E., & Gutiérrez‐Aguilar, R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00863 · Cited by 170
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“Several studies have provided evidence that Negr1 is involved in Alzheimer disease (AD) [69, 70], autism spectrum disorder (ASD) [27], and schizophrenia (SCZ) [71].”
Background
Metadata
- Authors
- Raghavan, N. S., Vardarajan, B., & Mayeux, R.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Corresponding author
- Mayeux, Richard
- Venue
- Neurology Genetics
- Published
- 2019-04
- Volume
- 5
- Issue
- 2
- Pages
- e310-e310
- ISSN
- 2376-7839 (ISSN-L)
- PMC
- PMC6395060
- OpenAlex
- W2903298416
- Cited by
- 33
- References
- 17
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 2
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Neurology Genetics (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (TL1TR001875)
- National Institute on Aging (U01AG032984, U24AG056270, U24AG021886)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, educational attainment, genetic risk factors, Mendelian randomization, single nucleotide polymorphisms, causal relationship, SSBP2, NEGR1, neuronal development, protective factors
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