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Genetic variations underlying Alzheimer's disease: evidence from genome-wide association studies and beyond
Cuyvers E, Sleegers K.. The Lancet. Neurology, 2016-07-01
Topic: Amyloid, tau and blood-test diagnosis
With the advent of genome-wide association studies (GWAS) and next-generation sequencing, more than 20 risk loci that affect Alzheimer's disease have been identified. These loci are estimated to explain about 28% of the heritability of liability, 30% of familial risk, and over 50% of sibling recurrence risk of developing Alzheimer's disease. These estimates are high in comparison with those for other complex diseases for which more risk loci have been discovered, such as type 2 diabetes, which is mostly a result of the strong effect of APOE ɛ4 and to a lesser extent the rare variant TREM2 p.Arg47His.
Key findings
- These loci are estimated to explain about 28% of the heritability of liability, 30% of familial risk, and over 50% of sibling recurrence risk of developing Alzheimer's disease.
- These estimates are high in comparison with those for other complex diseases for which more risk loci have been discovered, such as type 2 diabetes, which is mostly a result of the strong effect of APOE ɛ4 and to a lesser extent the rare variant TREM2 p.Arg47His.
- The search for functionally relevant genetic variants in risk loci detected in GWAS has revealed that the genetic variations underlying Alzheimer's disease include common variants affecting expression and splicing, a functional intragenic copy number variation, and rare pathogenic variants in risk loci, some of which might lead to familial Alzheimer's disease.
- An understanding of the contribution of these variants to the development of Alzheimer's disease has several clinical implications, including enhancing diagnostic accuracy and providing targets for the development of novel treatments.
Why it matters
This review reports that over 20 risk loci for Alzheimer's disease have been identified, with APOE ɛ4 having a strong effect and the rare TREM2 p.Arg47His variant a lesser one. It is a summary of genetic findings and does not offer a treatment, cure or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 51/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (The Lancet. Neurology) |
| Journal's citation record | 3 / 4 | The Lancet Neurology: journal h-index 457 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 286 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.8 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 5 / 6 | Cited 22.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 58 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Kristel Sleegers: h-index 81 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Antwerp: institution h-index 834 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27302364) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Cuyvers, E., & Sleegers, K. (2016). Genetic variations underlying Alzheimer's disease: evidence from genome-wide association studies and beyond. The Lancet. Neurology. https://doi.org/10.1016/s1474-4422(16)00127-7
Vancouver
Cuyvers E, Sleegers K. Genetic variations underlying Alzheimer's disease: evidence from genome-wide association studies and beyond. The Lancet. Neurology. 2016. doi:10.1016/s1474-4422(16)00127-7. PMID: 27302364.
BibTeX
@article{cuyvers2016-27302364,
author = {Cuyvers, E. and Sleegers, K.},
title = {{Genetic variations underlying Alzheimer's disease: evidence from genome-wide association studies and beyond}},
journal = {The Lancet. Neurology},
year = {2016},
doi = {10.1016/s1474-4422(16)00127-7},
pmid = {27302364},
url = {https://doi.org/10.1016/s1474-4422(16)00127-7}
}
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