Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.
The associations of rs3764650 with CSF Aβ<sub>1-42</sub>, t-tau and p-tau were analyzed in non-dementia AD, including preclinical and prodromal AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
Three common loci were confirmed to increase the risk of AD (rs3764650: OR = 1.20, 95% CI = 1.16-1.24; rs3752246: OR = 1.13,95% CI = 1.08-1.19; rs4147929: OR = 1.17, 95% CI = 1.10-1.24), but the associations varied among the different races.
A comprehensive literature search for studies involving the association between gene polymorphisms and AD was performed, and we finally selected 3 genes (4 polymorphisms) for the meta-analysis: ABCA7 (rs3764650), CD33 (rs3865444), and TOMM40 (rs157580, rs2075650).
An intronic low-frequency variant rs78117248 (minor allele frequency 3·8% in 58 patients with Alzheimer's disease and in controls 1·8% in 28 controls) showed strongest association with Alzheimer's disease (odds ratio 2·07, 95% CI 1·31-3·27; p=0·0016), and remained significant after conditioning for the GWAS top single nucleotide polymorphisms rs3764650, rs4147929, and rs3752246 (2·00, 1·22-3·26; p=0·006).
Recently, a large genome-wide association study has revealed that polymorphism of alleles and genotypes in rs3,764,650 within ABCA7 gene is associated with Alzheimer disease in whites.
We observed a significant association between rs3764650 and AD using the allele (P = 1.76E - 26, odds ratio (OR) = 1.21, 95 % confidence interval (CI) 1.17-1.26), dominant (P = 4.00E - 04, OR = 1.17, 95 % CI 1.07-1.28), recessive (P = 3.00E - 03, OR = 1.43, 95 % CI 1.13-1.81), and additive models (P = 3.00E - 03, OR = 1.49, 95 % CI 1.16-1.91).
Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden.
Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci.
Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.
To evaluate AD risk conferred by <i>ABCA7</i> rs4147929:G>A and <i>CD33</i> rs3865444:C>A, we used a large Spanish population (1796 AD cases, 2642 controls).
Including 178,304 individuals, the meta-analyzed odds ratio for Alzheimer's disease per one allele <i>ABCA7</i> rs4147929 increase was 1.15 (1.12-1.18).
Three common loci were confirmed to increase the risk of AD (rs3764650: OR = 1.20, 95% CI = 1.16-1.24; rs3752246: OR = 1.13,95% CI = 1.08-1.19; rs4147929: OR = 1.17, 95% CI = 1.10-1.24), but the associations varied among the different races.
Brain regions most significantly associated with AD risk variants were the left postcentral gyrus with ABCA7 (rs4147929, p = 4.45 × 10<sup>-6</sup>), right superior frontal gyrus by ZCWPW1 (rs1476679, p = 5.12 × 10<sup>-6</sup>), and right postcentral gyrus by APOE (p = 6.91 × 10<sup>-6</sup>).
An intronic low-frequency variant rs78117248 (minor allele frequency 3·8% in 58 patients with Alzheimer's disease and in controls 1·8% in 28 controls) showed strongest association with Alzheimer's disease (odds ratio 2·07, 95% CI 1·31-3·27; p=0·0016), and remained significant after conditioning for the GWAS top single nucleotide polymorphisms rs3764650, rs4147929, and rs3752246 (2·00, 1·22-3·26; p=0·006).
Large-scale genome-wide association studies (GWAS) have revealed that the ABCA7 rs3764650 polymorphism (or its proxies, namely rs115550680, rs3752246, and rs4147929) is associated with Alzheimer's disease (AD) susceptibility in individuals of Caucasian ancestry.
Our case-control study (416 AD patients and 302 controls) provides further data on the rs3752246 polymorphism in AD in the Hungarian population that has not been investigated so far regarding the ABCA7 gene variants.