Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil.
In addition, one variation, rs3851179, in the phosphatidylinositol binding clathrin assembly protein (PICALM) gene and one variation, rs6656401, in the complement component (3b/4b) receptor 1 (CR) gene were associated with AD.
We validated the risk for LOAD with BIN1 (rs744373), CR1 (rs6656401), and ABCA7 (rs376465), as well as the protective association for MS4A6A (rs610932) and CLU (rs11136000) variants.
Overall, the pooled data showed that the CR1 rs6656401 polymorphism was significantly associated with LOAD risk in the overall population (A vs. G: OR=1.32, 95%CI=1.17-1.50, P=0.000; AG+AA vs. GG: OR=1.39, 95%CI=1.20-1.61, P=0.000).
Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970-rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk.
We found by multivariate logistic regression analysis, that single nucleotide polymorphisms (SNPs) in CR1 (rs6656401 adjusted allelic p = 0.035; adjusted genotypic p = 0.043) and CLU (rs2279590 adjusted allelic p = 0.035; adjusted genotypic p = 0.006; rs11136000 adjusted allelic p = 0.038; adjusted genotypic p = 0.009) were significantly different between LOAD patients and nondemented controls.
The most significant single-nucleotide polymorphisms in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association with LOAD.
In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects.
Logistic analysis revealed that the rs116806486 polymorphism remained associated with LOAD in a dominant model, whereas the rs6691117 polymorphism was associated with LOAD in additive and recessive models but not in a dominant model after adjusting for sex, age at onset, and APOE ε4 status.
Examination of the haplotypes identified the risk of a 3-SNP (rs2274567, rs3737002, and rs6691117) haplotype "ATG" in CR1 was associated with an increased risk for LOAD.
Examination of the haplotypes identified the risk of a 3-SNP (rs2274567, rs3737002, and rs6691117) haplotype "ATG" in CR1 was associated with an increased risk for LOAD.
Examination of the haplotypes identified the risk of a 3-SNP (rs2274567, rs3737002, and rs</span>6691117) haplotype "ATG" in CR1 was associated with an increased risk for LOAD</span>.
Using 1709 subjects (697 deceased) from the Religious Orders Study and the Rush Memory and Aging Project, we tested 41 single-nucleotide polymorphisms (SNPs) within the linkage disequilibrium block containing the published CR1 AD SNP (rs6656401) for associations with episodic memory decline, and then examined the functional consequences of the top result.
It did not explain (part of) the association of genome wide association top single-nucleotide polymorphisms rs3818361/rs6656401, nor of the CR1 CNV, with AD in our cohort, whereas the CR1 CNV and rs3818361/rs6656401 represented the same association signal.
Our prevalent case study comparing prevalent AD cases (n = 428) with participants with no cognitive impairment (n = 524) revealed a significant association of rs6656401 and rs3818361 (CR1), rs2075650 (TOMM40), rs7561528 (BIN1), and rs3865444 (CD33) with late-onset AD that were robust to adjustment with age and apolipoprotein E ε4 genotype.
Here, we show that two Alzheimer's disease-associated CR1 variants, rs6656401 and rs3818361, are associated with major recurrent depression in females in a population-based cohort using individuals from the Generation Scotland: Scottish Family Health Study.
Gene-brain structure associations of 3 recently discovered risk genes for Alzheimer's disease, CLU (rs11136000C>T), CR1 (rs6656401G>A), and PICALM (rs3851179G>A), were investigated in 2 independent cohorts of young healthy adults (n = 430 and n = 492, respectively).
A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians.
We investigated the influence of the rs6656401 single nucleotide polymorphisms (SNP) of the CR1 gene, the rs3851179 SNP of the PICALM gene, and the rs11136000 SNP of the CLU gene on risk of AD in a Polish population.