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Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1
Wang Z, Lei H, Zheng M, Li Y, Cui Y, Hao F.. Molecular neurobiology, 2015-11-27
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
The genetic variants play a crucial role in the pathogenesis of Alzheimer's disease (AD), while the relationships of specific single nucleotide polymorphisms (SNPs) with AD are still controversial. We performed the meta-analysis to obtain a more precise estimation of whether growth factor receptor-bound protein-associated binding protein 2 (GAB2), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1) variants are associated with AD. Databases including PubMed, Embase, and Cochrane Library were searched to find relevant studies. Cochran's Q-statistic and I 2 were used to assess the heterogeneity among the included studies. Odds ratios (OR) and 95 % confidence intervals (95 % CIs) were conducted to evaluate the association between the SNP and the susceptibility to AD. Publication bias was estimated by funnel plots. All of the statistical analyses were implemented using R Version 3.2.1 software. A total of 35 case-control studies involving 15 SNPs were included. There was no significant association between SNPs of GAB2 rs2373115 (G > T) and PICALM rs541458 (C > T) and AD. The allele T of rs3851179 in PICALM was associated with a 13 % increase in the risk of AD. Seven SNPs on SORL1 were significantly associated with AD. Four SNPs, including rs1010159*T, rs641120*A, rs668387*T, and rs689021*A, were associated with a decreased risk of AD, while the other three SNPs, including rs12285364*T, rs2070045*G, and rs2282649*T, were all associated with an increased risk of AD. The results of the present study suggested that multiple gene variants were associated with AD. The SNP of rs3851179 (PICALM), rs12285364 (SORL1), rs2070045 (SORL1), and rs2282649 (SORL1) was associated with an increased risk of AD, whereas SORL1 rs1010159, rs641120, rs668387, and rs689021 were associated with a decreased risk of AD.
What this study adds
Evidence grade: High
This is a pooled review of 35 participants. Pooling 35 case-control studies covering 15 genetic variants, this meta-analysis found that variants in PICALM and SORL1 were linked to Alzheimer's risk, while the GAB2 variant rs2373115 was not. The T allele of PICALM rs3851179 was associated with a 13 % increase in risk, and seven SORL1 variants were tied to either higher or lower risk.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wang, Z., Lei, H., Zheng, M., Li, Y., Cui, Y., & Hao, F. (2016). Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1. Molecular neurobiology. https://doi.org/10.1007/s12035-015-9546-y
Vancouver
Wang Z, Lei H, Zheng M, Li Y, Cui Y, Hao F. Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1. Molecular neurobiology. 2016. doi:10.1007/s12035-015-9546-y. PMID: 26611835.
BibTeX
@article{wang2016-26611835,
author = {Wang, Z. and Lei, H. and Zheng, M. and Li, Y. and Cui, Y. and Hao, F.},
title = {{Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1}},
journal = {Molecular neurobiology},
year = {2016},
doi = {10.1007/s12035-015-9546-y},
pmid = {26611835},
url = {https://doi.org/10.1007/s12035-015-9546-y}
}
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.
Key findings
- We performed the meta-analysis to obtain a more precise estimation of whether growth factor receptor-bound protein-associated binding protein 2 (GAB2), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1) variants are associated with AD.
- There was no significant association between SNPs of GAB2 rs2373115 (G > T) and PICALM rs541458 (C > T) and AD.
- The allele T of rs3851179 in PICALM was associated with a 13 % increase in the risk of AD.
- Seven SNPs on SORL1 were significantly associated with AD.
- Four SNPs, including rs1010159*T, rs641120*A, rs668387*T, and rs689021*A, were associated with a decreased risk of AD, while the other three SNPs, including rs12285364*T, rs2070045*G, and rs2282649*T, were all associated with an increased risk of AD.
Why it matters
Pooling 35 case-control studies covering 15 genetic variants, this meta-analysis found that variants in PICALM and SORL1 were linked to Alzheimer's risk, while the GAB2 variant rs2373115 was not. The T allele of PICALM rs3851179 was associated with a 13 % increase in risk, and seven SORL1 variants were tied to either higher or lower risk. These are risk associations, so they help map who may be more susceptible rather than point directly to a treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designmeta-analysis
- Participants35
- Evidence strengthHigh
How this study scored 54/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurobiology) |
| Journal's citation record | 2 / 4 | Molecular Neurobiology: journal h-index 176 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 1 / 4 | 35 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | 4 / 7 | Cited 49 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.1 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 1 / 6 | Cited 0.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Fang Hao: h-index 11 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Linyi People's Hospital: institution h-index 132 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26611835) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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