Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1

Abstract

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 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.

Genes associated with Alzheimer's disease: an overview and current status

“… 84 Meta-analysis of the association between variants in SORL1 and AD has identified that SNP rs12285364 was significantly associated with increased risk of AD. 90 …”

Genetic Variants in SNCA and the Risk of Sporadic Parkinson’s Disease and Clinical Outcomes: A Review

“…The two most consistent genes for susceptibility to sporadic PD are the alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes, which can exert independent or joint effects on the risk of PD [56, 59, 61, 62, 87]. In addition, variants in other genes previously linked with autosomal forms (LRRK2, PARK16–18, and GBA) have also shown association with PD risk [64, 88–90].…”

Association between SORL1 polymorphisms and the risk of Alzheimer’s disease

“…Previous studies have revealed significant association between rs668387 and AD susceptibility [31][32][33][34][35]. Further, a meta-analysis by Wang et al [36] based on 35 studies suggested that SNP (rs668387, rs641120) has a decreased risk on AD susceptibility. However, Olgiati et al [37] found that there was no significant association between rs668387 and AD as was also supported by the current metaanalysis results.…”