Association of the CR1 polymorphism with late-onset Alzheimer's disease in Chinese Han populations: A meta-analysis

It is well known that genetic variants play a critical role in the pathogenesis of Alzheimer's disease (AD). In 2009, a genome-wide association study (GWAS) demonstrated that a single nucleotide polymorphism (SNP), rs6656401, in complement receptor 1 (CR1) is significantly associated with late-onset Alzheimer's disease (LOAD) in Caucasian population. Subsequently, other researchers have attempted to validate this finding in Chinese Han populations. However, these findings in Chinese Han populations have produced both negative and positive results. To derive a more precise estimation for the relationship, we performed the present meta-analysis by analyzing three published association studies involving CR1 SNP rs6656401 through the use of the RevMan (v.5.1) program. Pooled odds ratios (ORs) were calculated for allele contrasts (A vs. G) and a dominant model [(AA + AG) vs. GG] in three studies that included 1019 cases and 1080 controls, respectively. The statistical results showed a significant difference between patients and controls for the A allele of CR1 SNP rs6656401 (P = 0.005). In addition, carriers of the A allele (AA + AG) of rs6656401 had a 1.69-fold increased risk for LOAD compared with non-carriers (GG) (P = 0.01). In conclusion, despite there are some limitations, this meta-analysis indicates that the A allele of the CR1 SNP rs6656401 is significantly associated with LOAD susceptibility in Chinese Han populations.     

Different implication of NEDD9 genetic variant in early and late-onset Alzheimer's disease

Alzheimer's disease (AD) is a complex and multifactorial progressive neurodegenerative disease. Recently, two studies reported inconsistent results on a possible involvement of the NEDD9 (neural precursor cell expressed, developmentally down-regulated 9, 6p25-p24) as a candidate gene for the risk of developing AD and/or Parkinson's disease (PD). We analyzed the distribution of the rs760678 SNP polymorphism in 735 Italian subjects: 214 unrelated sporadic late-onset AD patients (LOAD, 64.5% females, mean age-at-onset 71.8 ± 5.2 years), 135 early-onset AD patients (EOAD, 57.3% females, mean age-at-onset 57.5 ± 5.5 years) and 386 healthy controls (68.9% females, mean age 83.4 ± 17.9 years; SD). We observed a statistically significant difference between LOAD patients and controls according to genotypes (P = 0.016) and allele frequency (P = 0.007); CC genotype was more frequent in LOAD cases (44.4%) than controls (36.0%). No difference after stratification of the data in terms of gender and status of the APOE ?4 allele was observed. In conclusion, our data do support an implication of the NEDD9 allelic variant in late-onset AD, with an independent effect of the apolipoprotein E (APOE) ?4 allele in the risk of developing AD.     

Lack of association between rs597668 polymorphism near EXOC3L2 and late-onset Alzheimer's disease in Han Chinese

Recently, an international genome-wide association study (GWAS) additionally found rs597668 near EXOC3L2/BLOC1S3/MARK4 was a new genome-wide significance locus associated with late-onset Alzheimer's disease (LOAD) in Caucasians. Follow-up replication studies were conducted almost exclusively in Caucasians, and the effects of the risk locus in other populations are as yet unknown. This study investigated the GWAS-associated locus near EXOC3L2 in 1205 unrelated Northern Han Chinese subjects comprising 598 LOAD patients and 607 healthy controls matched for gender and age. The results showed no significant differences in the genotypic or allelic distributions of rs597668 polymorphism between LOAD cases and healthy controls (genotype: P = 0.653; allele: P = 0.603), even after stratification for apolipoprotein E (APOE) ?4 status and statistical adjustment for age, gender and APOE ?4 status. This study suggests that the rs597668 polymorphism near EXOC3L2 may not play a major role in the susceptibility to LOAD in the Northern Han Chinese population.     

Association study on the NAPG gene and bipolar disorder in the Chinese Han population

Background: Bipolar disorder is a mental health problem throughout the world. Chromosome 18p11 has been identified by several studies as a susceptiblilty region for bipolar disorder and NAPG, located on 18p11, has been suggested as being associated with bipolar disorder in European population. Methods: Our study employed five SNPs (rs2290279, rs495484, rs510110, rs617040 and rs473938) to investigate the role of NAPG in the Chinese Han population based on a sample of 465 controls vs. 499 bipolar patients. Results: Rs617040 was excluded from further analysis because of deviation from Hardy–Weinberg equilibrium. Rs473938 and rs2290279 showed significant association in both allele and genotype frequencies (rs473938: allele p = 0.0028 after 100,000 permutations, genotype p = 0.0018; rs2290279: allele p = 0.0042 after 100,000 permutations, genotype p = 0.0028). Several combinations of haplotype were found to be associated with bipolar disorder. Haplotype T–A–T of rs473938–rs2290279–rs495484 was defined by confidence intervals algorithm and had a p value of 0.0038 after 100,000 permutations. Conclusions: Our study supports NAPG as a candidate for susceptibility to bipolar disorder.     

Association between promoter polymorphisms in anterior pharynx-defective-1a and sporadic Alzheimer's disease in the North Chinese Han population

Amyloid β-peptide (Aβ) deposition in brain is important in the development of sporadic Alzheimer's disease (SAD) and Aβ is produced through sequential cleaving of amyloid precursor protein (APP) by β-secretase and γ-secrease. Anterior pharynx-defective-1 (APH-1) is an important subunit of the gamma-secretase complex, and its expression level was associated with the activity of γ-secrease. We hypothesized that alterations in the APH-1 promoter region might alter APH-1 expression and the activity of γ-secrease, thus be involved in the SAD process. In the present study, we sequenced APH-1a promoter region in 20 randomly selected controls and 20 SAD patients and detected two polymorphisms which were −980C/G (rs3754048) and −21C/A (rs2275780). Then, we investigated genotypes and allele of these two polymorphisms as well as apolipoprotein ?4 (APOE ?4) status in 256 SAD patients and 276 normal controls with restriction fragment length polymorphisms analysis and sequencing. Results showed the GG genotype and G allele of −980C/G polymorphism were more frequent in the SAD group than that in the controls not only in the whole subjects (genotype P = 0.038, allele P = 0.01 respectively) but also in the APOE ?4 + subjects (genotype P = 0.048, allele P = 0.016 respectively). There was no statistical difference between SAD group and controls regarding to the frequency of alleles and genotypes of −21C/A whenever before or after stratification by APOE ?4. Our results suggest that there is an association between −980C/G and the development of SAD in the Northern Han Chinese population and that allele G may interact synergistically with the APOE ?4 allele to increase the risk of SAD.     

Association analysis of the paraoxonase-1 gene with Alzheimer's disease

Genetic variants in the paraoxonase (PON) gene cluster, particularly a single C/T promoter polymorphism (rs 705381) in the PON-1 gene, have recently been associated with Alzheimer's disease (AD). The T allele, in particular, presents an increased risk for the development of AD. Here, we investigate the potential role of this polymorphism in an Italian case-control population consisting of 306 sporadic AD patients and 275 controls, and also evaluate a possible interaction with the ApoE genotype. No association between the PON-1 polymorphism and AD was observed. The T allele frequency was slightly over-represented in AD patients compared to the controls, but this was far from being statistically significant. Our sample was evaluated to have 97.3% power to detect an OR of 2.0 (64.3% power with OR = 1.5) at an α level of 0.05. No evidence of an interaction between the T risk-allele and the ApoE ?4 allele status and no effect of the PON-1 polymorphism on age at onset was detected. Our results do not support other studies indicating that the PON-1 promoter polymorphism plays a major role in AD, suggesting that other large studies are necessary to further elucidate the effect of PON on the development of the disease in the general population.     

Tau-tubulin kinase-1 gene variants are associated with Alzheimer's disease in Han Chinese

Tau-tubuline kinase 1 (TTBK1) is a recently discovered brain-specific protein kinase involved in tau phosphorylation at AD-related sites. A recent large study has identified significant association of two single nucleotide polymorphisms (SNPs) (rs2651206 and rs7764257) in the TTBK1 gene with late-onset Alzheimer's disease (LOAD) in Spanish. Here, we performed a case–control study to clarify whether the risk for LOAD might be influenced by these polymorphisms in a large Chinese cohort consisting of 400 patients and 388 healthy controls. The minor alleles of the rs2651206 polymorphism within TTBK1 was significantly associated with a reduced risk of LOAD (odds ratio/OR = 0.69, P = 0.011). Furthermore, rs2651206 polymorphism was still strongly associated with LOAD (OR = 0.72, P = 0.05) after adjusted for age, gender, and the apolipoprotein E (APOE) ?4 status. Haplotype analysis identified the TG haplotype, deriving from the two minor alleles, to decrease the risk of LOAD (OR = 0.78, P = 0.037). This study provides the evidence that variations in the TTBK1 gene may play an important role in the pathogenesis of sporadic LOAD in a Han Chinese population.     

Endothelin-Converting Enzyme-1 Promoter Polymorphisms and Susceptibility to Sporadic Late-Onset Alzheimer's Disease in a Chinese Population

Endothelin converting enzyme (ECE-1) is a candidate Alzheimer disease susceptibility gene. It was previously reported that western individuals homozygous for the C-338A polymorphism (AA) within the ECE1 gene promoter region are at reduced risk of developing late onset Alzheimer disease (LOAD). A further polymorphism, T-839G, is present within the ECE1 promoter region but a potential association with LOAD has not been studied. We therefore studied possible associations between these ECE1 polymorphisms and LOAD in a Chinese population. Subjects comprised 376 Chinese LOAD patients and 376 age- and sex-matched controls; all subjects were typed for the ECE1 C-338A and the T-839G polymorphisms. We report that the frequency of the 338A allele was decreased in LOAD patients compared to controls (adjusted OR =0.73; 95% CI=0.54–0.98; P=0.03). There was no significant association between T-839G genotype and LOAD, however the combined 839T/338A haplotype was significantly associated with decreased risk of LOAD (OR=0.73; 95% CI=0.57–0.93; P=0.01). This study argues that the ECE1 338A allele is protective against LOAD in a Chinese population.     

Lack of association between PICALM rs3851179 polymorphism and Alzheimer's disease in Chinese population and APOEε4-negative subgroup

Recently, the association between PICALM rs3851179 polymorphism and Alzheimer's disease (AD) was investigated in the Chinese population by 3 independent studies. However, both allele and genotype tests failed to reveal any association. The association was identified only in the APOEε4-negative subgroup. We think that the failure to replicate the association may be because of the relatively small sample size. In this research, we reinvestigated the association using all the samples from these 3 studies (n = 2486, and 1202 cases and 1284 control subjects). We failed to replicate this association between the rs3851179 polymorphism and AD in all samples and the APOEε4-negative subgroup. Our results indicate that rs3851179 may not be an AD susceptibility locus in the Chinese population and the APOEε4-negative subgroup.     

Association between STAT5 polymorphisms and glioblastoma risk in Han Chinese population

The aim of this study was to investigate the associations between STAT5 gene polymorphisms and glioblastoma (GBM) risk predisposition. We undertook a case–control study to analyze two STAT5 polymorphisms (STAT5a rs11079041 and STAT5b rs2293157) in a Han Chinese population, by extraction of genomic DNA from the peripheral blood of 328 patients with glioma and 342 control participants, and performed STAT5 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in STAT5a rs11079041. Nevertheless, STAT5b rs2293157 G/T genotype was at increased risk of glioma (P = 0.001). Furthermore, rs2293157T allele was more significantly prognostic in patients suffering from glioblastoma compared to other subtypes of gliomas (P < 0.001; odds ratio (OR) = 5.14, CI 95%: 2.70–9.79). These findings led us to conclude that polymorphism in STAT5b rs2293157 G/T was observed to be associated with susceptibility of glioblastoma. Nevertheless, further investigation with a later confirmation in another ethnical or geographical cohort is required.     

Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease

Vascular risk factors have been implicated in the pathogenesis of vascular dementia and Alzheimer's disease. The identification of a novel vascular disease susceptibility locus at 9p21.3 has recently generated great interest. In the present study, we sought to determine whether a common genetic variant (tagged by rs1333049, G/C) in the 9p21.3 locus—that has been previously linked to an increased vascular risk—might influence the susceptibility to vascular dementia (VaD) and late-onset Alzheimer's disease (LOAD). A cohort of 200 VaD patients, 407 LOAD patients and 405 cognitively healthy controls were genotyped for rs1333049 using a fluorogenic 5′ nuclease assay. The frequency of the C allele of rs1333049 was significantly higher in VaD (62.2%, P = 0.005) and LOAD (60.7%, P = 0.004) patients than in controls (53.6%). After adjustment for the APOE ε4 carrier status and other vascular risk factors, the C allele of rs1333049 remained significantly associated with both VaD (OR 1.31, 95% CI 1.07-1.77, P < 0.01) and LOAD (OR 1.28, 95% CI 1.04-1.55, P < 0.01). Altogether, our data indicate for the first time that the C allele of rs1333049 in the vascular disease susceptibility locus is associated with VaD and LOAD, independent of traditional risk factors and the APOE ε4 genotype.     

Association analysis of GRIN1 and GRIN2B polymorphisms and Parkinson's disease in a hospital-based case–control study

Hyperactivation of N-methyl-d-aspartate receptors (NMDARs) leads to neuronal excitotoxicity and is suggested to play a role in many brain disorders, including Alzheimer's disease and schizophrenia. However, the association between polymorphisms in the genes that code for NMDAR subunits, N-methyl-d-aspartate 1 and 2B (GRIN1 and GRIN2B) and Parkinson's disease (PD) remains unclear. In a hospital-based case–control study of PD, DNA samples were collected from 101 PD patients and 205 healthy controls. Genotyping assays were used to screen for polymorphisms in the GRIN1 (rs2301364 T > C, rs28489906 T > C, and rs4880213 T > C) and GRIN2B (C366G, C2664T, and rs1805476 T > G) genes, and logistic regression analysis was then used to assess the association between these single nucleotide polymorphisms (SNPs) and PD susceptibility. None of the 6 SNPs were significantly associated with PD risk on their own. However, in conjunction with putative low-risk genotypes for the GRIN1 gene, the GRIN2BC366G variant was significantly associated with reduced PD risk compared with the homozygous genotype 366CC (OR = 0.38, 95%CI = 0.17–0.93, P = 0.033). A synergistic effect on risk reduction was observed in subjects who carried multiple polymorphisms of GRIN1 and the GRIN2BC366G polymorphism (OR = 0.78, 95%CI = 0.59–1.02, P_trend = 0.073). Our results suggest that polymorphisms in the GRIN1 and GRIN2B genes may serve as potential biomarkers for a reduced risk of PD among the Chinese population in Taiwan.     

CX3CR1 polymorphisms and the risk of age-related macular degeneration

Background: Age-related macular degeneration (AMD), a most common eye disease, can lead to irreversible visual impairment. Age, genetic and environmental factors have been implicated in AMD. Chemokine (C-X3-C motif) receptor 1 (CX3CR1) gene polymorphisms could influence the susceptibility of AMD. Methods: We tested the association between AMD and single nocleotide polymorphisms (SNPs) of CX3CR1 gene (rs3732378 and rs3732379) in 102 cases and 115 controls from China. Genotypes were determined by MassArray genotyping assay method. Association between CX3CR1 gene polymorphisms and AMD were examined by χ² test and logistic regression. Results: Genotype distribution of CX3CR1 gene polymorphisms were in accordance with HWE examination. No obvious differences were observed in the genotypes of rs3732378 polymorphism between case and control groups (P>0.05), but A allele of it could increase the risk of AMD (P=0.025, OR=2.391, 95% CI=1.092-5.237). Both TT genotype and T allele of rs3732379 were significantly associated with the susceptibility of AMD (P=8.663, OR=8.663, 95% CI=1.044-71.874; P=0.021, OR=2.076, 95% CI=1.104-3.903). Age, gender and smoking status were used as common confounders to adjust the association between CX3CR1 gene polymorphism and AMD risk. Then we found that rs3732378 had no obvious association with AMD susceptibility. TT genotype of rs3732379 related to the occurrence of AMD, but the association was not significant (P=0.050, OR=8.274, 95% CI=1.002-69.963). T allele of rs3732379 might increase the susceptibility of AMD (P=0.029, OR=2.033, 95% CI=1.077-3.838). Conclusion: T allele of rs3732379 might have a positive association with the susceptibility of AMD.     

Supportive evidence for neuregulin 1 as a susceptibility gene for schizophrenia in a Japanese population

Schizophrenia is a complex genetic disorder and affects approximately 1% of the population worldwide. Recently, Stefansson et al. identified neuregulin 1 (NRG1) on 8p12 as a susceptibility gene for schizophrenia in the Icelandic population. It was reported that the at-risk haplotype (“Hapice”) constructed from five SNPs and two microsatellite markers was found to be over-represented in patients with schizophrenia compared to controls. Since then several independent studies have supported the association of NRG1 with schizophrenia. We performed a case–control association study using the four SNPs in a Japanese sample. We genotyped three SNPs (SNP8NRG221533, SNP8NRG241930, and SNP8NRG243177) from Stefansson et al. and one SNP (rs1081062) located in intron 1 of NRG1. There were no significant differences in allele frequencies for each SNP between cases and controls, however, homozygotes of minor alleles in SNP8NRG241930, SNP8NRG243177, and rs1081062 were associated with an increased risk of schizophrenia (P = 0.025, OR = 4.14; P = 0.041, OR = 1.43; and P = 0.0023, OR = 3.06, respectively). Furthermore, the haplotype constructed from four SNPs shows a significant association with schizophrenia (permutation P = 0.026). Our data support the hypothesis that NRG1 gene is a susceptibility gene for schizophrenia.     

The interleukin-6 gene −572C/G promoter polymorphism modifies Alzheimer's risk in APOE ɛ4 carriers

Inflammatory response is involved in the etiopathology of Alzheimer's disease (AD). Interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, was reported to be associated with both increased Aβ aggregation and the appearance of hyperphosphorylated tau in AD brain. To explore the association of genetic variants in the promoter of IL-6 gene with sporadic AD (SAD), a case–control study was conducted in a North Chinese Han population. A systematic screening of IL-6 promoter was performed using direct sequencing and two polymorphisms were obtained including −572C/G (rs1800796) and −384A/T (rs7802308). Definitive genotyping of these markers and apolipoprotein E (APOE) polymorphism were surveyed in 341 SAD patients and 421 controls. The results revealed no significant differences in the distributions of alleles or genotypes between SAD and control groups. However, there was an interaction between −572C/G and APOE genotypes (P = 0.016) using logistic analysis. In the subjects with APOE ?4, there were significant differences in the allele (P = 0.004) and genotype (P = 0.004) distributions of −572C/G polymorphism between SAD and control groups. The −572CC genotype increased risk for AD by 3.301-fold (Wald = 11.093, adjust OR = 3.301, 95% CI = 1.635–6.665, P = 0.001) compared to CG + GG genotype. The present results suggest the −572 polymorphism could modify the risk for SAD in APOE ?4 carriers.     

Association of GPR50, an X-linked orphan G protein-coupled receptor,and affective disorder in an independent sample of the Scottish population

A recent report detected association between GPR50, an orphan G protein-coupled receptor, and bipolar disorder (BD) in the Scottish population [29]. We sought to replicate this study in a second sample from the same population, consisting of 338 patients with BD, 359 patients with major depressive disorder (MDD) and 913 control individuals. In addition, the effect of GPR50 genotype on clinical phenotype and treatment response was assessed in a subset of 56 patients with early onset MDD (eoMDD). We identified an association with BD in women with an intronic SNP, rs1202874, that withstood correction for multiple testing (p = 0.0035, permuted p = 0.037, OR = 1.9, 95%CI 1.2–3.0). However, we failed to find an association with the previously associated Δ502-505 polymorphism (p = 0.2). Combined analysis of this and the original samples did detect association between the deletion and susceptibility to BD in females, but with a reduced effect size (p = 0.0006, permuted p = 0.0024, OR = 1.41, 95%CI 1.16–1.71). In the highly phenotyped eoMDD subgroup, we found an association between the Δ502-505 deletion polymorphism and age of onset (p = 0.049), number of episodes (p = 0.044), hypomanic symptoms (p = 0.019), and initial thinking time (p = 0.027), in women; and in family history of depression in men (p = 0.038), uncorrected for multiple testing. No association was seen between Δ502-505 genotype and treatment response at 3 months. To our knowledge this is the first association of rs1202874 with BD and is the second positive association at the GPR50 locus.     

Screening for two SNPs of LINGO1 gene in patients with essential tremor or sporadic Parkinson's disease in Chinese population

Two markers rs9652490 and rs11856808 both located in intron 3 of the LINGO1 gene have been nominated recently to be associated with essential tremor (ET). Although ET and Parkinson's disease (PD) are considered as different entities, they have many overlapping clinical and pathological features. We aimed to evaluate the role of rs9652490 and rs11856808 in the development of ET and PD. To this point, we sequenced the region involving the two markers in 109 ET cases, 425 sporadic Parkinson's disease (SPD) cases and 430 controls in Chinese population. After stratification by age, the rs9652490G allele suggested protective role in the early onset PD (EOPD, age at onset ≤50 years) group compared with age matched controls (OR = 0.56, 95% CI: 0.35–0.90, p = 0.015). No other significant association was found. We concluded that the two markers rs9652490 and rs11856808 were not strongly related to the development of ET or late onset SPD, but the rs9652490G allele might be a protective factor for EOPD in Chinese population.     

Is KIF24 a genetic risk factor for Frontotemporal Lobar Degeneration?

Linkage analysis identified a region on chromosome 9p associated with Frontotemporal Lobar Degeneration (FTLD). A detailed analysis of candidate genes lying in this region demonstrated an association with Ubiquitin Associated Protein (UBAP)1. The distribution of five Single Nucleotide Polymorphisms (SNPs) located in the chromosome 9 haplotype identified via linkage analysis, including UBAP1 rs7018487, UBAP2 rs1785506 and rs307658, and KIF24 rs17350674 and rs10814083, has been determined in a population of 284 patients diagnosed with FTLD, including 245 with behavioural variant Frontotemporal Dementia (bvFTD), 23 with Progressive Aphasia and 16 with Semantic Dementia, compared with 318 age-matched controls. A statistically significant increased frequency of the KIF24 rs17350674 AA genotype was observed in patients compared with controls (7.4 versus 2.5%; P = 0.0068, OR: 3.63, CI: 1.58–8.35). Considering each syndrome separately, similar results where obtained in bvFTD versus controls (7.7 versus 2.5%, P = 0.005, OR: 3.26, CI: 1.40–7.57). Stratifying for gender, a statistically significant increased genotypic frequency was observed in female patients as compared with female controls (8.9 versus 2.5%, P = 0.008, OR: 3.85, CI: 1.36–10.93). In silico analysis predicted that the substitution from W to L caused by the rs17350674 affects protein function (P < 0.05). The KIF24 rs17350674 polymorphism likely acts as a risk factor for sporadic FTLD, but a replication study would be needed to confirm these preliminary findings.     

Association between somatostatin gene polymorphisms and sporadic Alzheimer's disease in Chinese population

Recent evidence has suggested that down-regulation of somatostatin (SST) expression in the human brain during early stages of aging leads to an elevation in the steady-state levels of Aβ and therefore may be involved in Alzheimer's disease (AD) progression. We hypothesized that alterations in the SST gene might alter its expression or function and also play a role in the pathogenesis of sporadic AD (SAD). First, we sequenced the entire SST gene in 25 randomly selected controls and 25 SAD patients and then screened for C/T polymorphisms (rs4988514) in the 3′ un-translated region. We genotyped rs4988514 polymorphisms as well as apolipoprotein ?4 (APOE ?4) status in 309 SAD patients and 276 normal controls with restriction fragment length polymorphism (RFLP) analysis. Results showed that the C allele of the rs4988514 polymorphism had an increased incidence in the SAD group compared to the control group (p = 0.042). In subjects with the APOE ?4 allele, the presence of both the CC genotype and the C allele of this polymorphism were elevated in the SAD group compared to the control group (genotype p = 0.027, allele p = 0.011). In the whole study group, the age, sex, and APOE ?4 adjusted OR for the risk of AD in C allele carriers was 1.313 (95%CI = 1.068–2.234, p = 0.027) whereas within only APOE ?4 allele carriers, the adjusted OR increased to 2.734 (95%CI = 1.236–5.862, p = 0.012). Our results supported the notion that the C allele of the rs4988514 polymorphism may increase the risk for AD in the Chinese population and possibly have additive effect with the APOE ?4 allele.     

Polymorphisms of CR1, CLU and PICALM confer susceptibility of Alzheimer's disease in a southern Chinese population

In this case-controlled study, we tested susceptible genetic variants for Alzheimer's disease (AD) in CR1, CLU and PICALM from genome-wide association studies (GWAS) in a southern Chinese population. Eight hundred twelve participants consisting of 462 late-onset Alzheimer's disease (LOAD) patients and 350 nondemented control subjects were recruited. 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. For PICALM, LOAD association was found only in the APOE ε4 (−) subgroup (rs3851179 adjusted allelic p = 0.028; adjusted genotypic p = 0.013). Our findings showed evidence of CR1, CLU, and PICALM and LOAD susceptibility in an independent southern Chinese population, which provides additional evidence for LOAD association apart from prior genome-wide association studies in Caucasian populations.