Triggering receptor expressed on myeloid cells 2 variants are rare in Parkinson's disease in a Han Chinese cohort

Recent studies have reported that a rare nonsynonymous variant rs75932628-T in the TREM2 gene is associated with increased risk of Alzheimer's disease and Parkinson's disease (PD) in European-descended populations. However, the association between rare TREM2 mutations and PD risk remains unknown in Chinese population. We directly sequenced exon2 of TREM2 in a cohort of 476 PD patients and 432 healthy controls from a Han Chinese population. Rs75932628-T (p.R47H) was found in 0.2% of PD cases (1/476) but in none of the controls (0/432, p = 1.000), with a minor allele frequency of 0.06% among the 908 subjects. Our findings suggest that variants in exon2 of TREM2 are extremely rare, and it is not a genetic risk factor for PD in the southern Han Chinese population.     

Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin Registry for Alzheimer's Prevention

Recent studies have found an association between a variant in triggering receptor expressed on myeloid cells 2 (TREM2) (rs75932628-T) and both Alzheimer's disease (AD) and cognitive function in individuals aged 80–100 years. The role of TREM2 in younger, asymptomatic individuals is unknown. We examined this variant in 1148 participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of middle-aged adults enriched for a parental history of AD. Thirteen individuals carried the T risk allele. Carriers were more likely to have a parental history of AD (100% of carriers vs. 70% of noncarriers; p = 0.01) and, among the parental history subset, families with a TREM2 carrier had a younger maternal age of AD onset than noncarriers (67.9 vs. 75.6 years; p = 0.03). There was no significant association between TREM2 carrier status and cognitive function or decline. In conclusion, the association between TREM2 and both parental history of AD and younger maternal age of AD onset provide additional support for the role of TREM2 in AD and illustrate the importance of considering family history in AD study design.     

Triggering receptor expressed on myeloid cells 2 variant is rare in late-onset Alzheimer's disease in Han Chinese individuals

Recent studies have reported that a rare mutation of triggering receptor expressed on myeloid cells 2 gene (TREM2 [rs75932628-T]) has significantly increased the risk of late-onset Alzhemier's disease (LOAD) in European-descendent population. To date, no study has investigated the association between rare mutations of TREM2 and LOAD risk in non-European population. Here, we sequenced exon2 of TREM2 in the northern Han Chinese population consisting of 1133 patients with LOAD and 1159 control subjects. Although, 4 novel mutations (c.102G>A: Val34Val, c.330C>T: Cys110Cys, c.342T>C: His114His, and c.343G>A: Gly115Ser) were identified in patients with LOAD, none of them exhibited significant association with LOAD risk after Bonferroni correction. Most importantly, the previously reported rare variants in European-descendent population including rs75932628-T (predicted to cause an R47H substitution) were absent in our cohort. These findings suggest that mutations in exon2 of TREM2 were unlikely to play a key role in the susceptibility of LOAD in the northern Han Chinese population.     

Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease

Recent evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease. TREM2 mutations are the genetic basis for a condition characterized by polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) and an early-onset dementia syndrome. TREM2 is important in the phagocytosis of apoptotic neuronal cells by microglia in the brain. Loss of function might lead to an impaired clearance and to accumulation of necrotic debris and subsequent neurodegeneration. In this study, we investigated a consanguineous family segregating autosomal recessive behavioral variant FTLD from Antioquia, Colombia. Exome sequencing identified a nonsense mutation in TREM2 (p.Trp198X) segregating with disease. Next, using a cohort of clinically characterized and neuropathologically verified sporadic AD cases and controls, we report replication of the AD risk association at rs75932628 within TREM2 and demonstrate that TREM2 is significantly overexpressed in the brain tissue from AD cases. These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease.     

Insulin-like growth factor 1 (IGF1) polymorphism is associated with Alzheimer's disease in Han Chinese

A review of pathogenic findings in Alzheimer's brains and the functional consequences of altered insulin-like growth factor 1 (IGF1) input to the brain suggest the association between Alzheimer's disease (AD) and the disrupted IGF1 signaling. Recently, the identification of polymorphism rs972936 that was associated with both an increased risk of AD and high circulating levels of IGF1 was reported in Southern European population. In order to evaluate the involvement of the IGF1 polymorphism in the risk of developing late-onset Alzheimer's disease (LOAD) in Chinese, we performed an independent case-control association study in a Han Chinese population (794 LOAD cases and 796 controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P = 0.006, allele P = 0.047). The T allele of rs972936 demonstrated a 1.16-fold risk for developing LOAD when compared with the C allele, which diverges to the report in the Caucasian population. After stratification by apolipoprotein E (APOE) ?4-carrying status, rs972936 polymorphism was only significantly associated with LOAD in non-ApoE ?4 allele carriers (genotype P = 0.002, allele P = 0.039). Multivariate logistic regression analysis also conferred this positive association between the SNP rs972936 and LOAD in the recessive and additive model after adjustment for age, gender, and the ApoE ?4 carrier status. These results suggest that IGF1 polymorphism has a possible role in changing the genetic susceptibility to LOAD in a Han Chinese population.     

Frontobasal gray matter loss is associated with the TREM2 p.R47H variant

A rare heterozygous TREM2 variant p.R47H (rs75932628) has been associated with an increased risk for Alzheimer's disease (AD). We aimed to investigate the clinical presentation, neuropsychological profile, and regional pattern of gray matter and white matter loss associated with the TREM2 variant p.R47H, and to establish which regions best differentiate p.R47H carriers from noncarriers in 2 sample sets (Spanish and Alzheimer's Disease Neuroimaging Initiative, ADNI1). This was a cross-sectional study including a total number of 16 TREM2 p.R47H carriers diagnosed with AD or mild cognitive impairment, 75 AD p.R47H noncarriers and 75 cognitively intact TREM2 p.R47H noncarriers. Spanish AD TREM2 p.R47H carriers showed apraxia (9 of 9) and psychiatric symptoms such as personality changes, anxiety, paranoia, or fears more frequently than in AD noncarriers (corrected p = 0.039). For gray matter and white matter volumetric brain magnetic resonance imaging voxelwise analyses, we used statistical parametric mapping (SPM8) based on the General Linear Model. We used 3 different design matrices with a full factorial design. Voxel-based morphometry analyses were performed separately in the 2 sample sets. The absence of interset statistical differences allowed us to perform joint and conjunction analyses. Independent voxel-based morphometry analysis of the Spanish set as well as conjunction and joint analyses revealed substantial gray matter loss in orbitofrontal cortex and anterior cingulate cortex with relative preservation of parietal lobes in AD and/or mild cognitive impairment TREM2 p.R47H carriers, suggesting that TREM2 p.R47H variant is associated with certain clinical and neuroimaging AD features in addition to the increased TREM2 p.R47H atrophy in temporal lobes as described previously. The high frequency of pathologic behavioral symptoms, combined with a preferential frontobasal gray matter cortical loss, suggests that frontobasal and temporal regions could be more susceptible to the deleterious biological effects of the TREM2 variant p.R47H.     

Lack of association between the functional c-kit rs6554199 polymorphism and achalasia in a Spanish population

A functional polymorphism (rs6554199) located in the c-kit gene was associated with achalasia in a Turkish cohort. Our aim was to replicate this result in a large cohort of Spanish patients and controls. A case-control study was performed with 282 Spanish white unrelated patients and 687 healthy controls. All were genotyped for SNP rs6554199 using a TaqMan Assay. No association was found in our study (T allele frequency in patients and controls: 47.3% vs. 49.4%; OR = 0.92, p = 0.41). The finding that the T allele of the c-kit rs6554199 polymorphism could be associated with achalasia as reported in a Turkish population could not be replicated in a Spanish cohort. Although ethnic differences might explain these data, the sample size that compromised the statistical power in the Turkish cohort and is higher in our study, led us to suggest that the reported association seems to be a false positive.     

Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study

Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. We genotyped R47H in 2974 samples (427 cases and 2540 control subjects) from the Cache County study using a custom TaqMan assay. We observed 7 heterozygous cases and 12 heterozygous control subjects with an odds ratio of 3.5 (95% confidence interval, 1.3–8.8; p = 0.0076). The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant.     

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.     

Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease

Replications of the association between APOE-ε4 allele load and regional brain atrophy in Alzheimer's disease (AD) patients hold promise for future studies testing relationships between other disease risk gene variants and brain structure. A polymorphism, rs10868366, in the Golgi phosphoprotein 2 gene, GOLM1, was recently identified as an AD risk factor in a genome-wide association study. In a subset of the same AD cohort, we used voxel-based morphometry to test for association between the disease risk genotype and reduced regional gray matter (GM) volume in AD patients (n = 72). A mean 14% reduction in GM volume was observed in the left frontal gyrus with the higher risk GG genotype. A similar association was observed in an independent, dataset of nondemented subjects (n = 278), although with a smaller effect (1%). This replicated association with GM structural variation suggests that GOLM1 polymorphisms may be related to cognitive phenotypes. The greater effect size in AD patients also suggests that the GG genotype could be a risk factor for the expression of cognitive deficits in AD.     

Genetic variation in APOE cluster region and Alzheimer's disease risk

We report the fine mapping/sequencing results of promoter and regulatory regions of APOE cluster genes (APOE, APOC1, APOC4, APOC2, and TOMM40) in Alzheimer's disease (AD) risk as well as in the progression from mild cognitive impairment (MCI) to AD. Long-range sequencing in 29 MCI subjects who progressed to dementia revealed 7 novel variants. Two potentially relevant novel variants and 34 single nucleotide polymorphisms (SNPs) were genotyped in a large sample of AD, MCI, and control subjects (n = 1453). Globally, very little association signal was observed in our sample in the absence of APOE ε4. Rs5158 (APOC4 intron 1) and rs10413089 (3′ to APOC2) showed a trend toward an increase in AD risk independently from APOE ε4 associated risk though it did not survive multiple test correction (uncorrected p = 0.0099 and 0.01, respectively). Interestingly, rs10413089 showed a similar effect in an independent series. The analysis of the discovery sample showed an association of TOMM40 single nucleotide polymorphisms with progression from MCI stage to AD (rs59007384 and rs11556510), as well as with a shorter time to progression from MCI status to AD (rs10119), though these results could not be replicated in independent series. Further studies are needed to investigate the role of APOE cluster variants in AD risk.     

Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk

Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (P_{Mantel–Haenszel,} odds ratio (OR)_M–H (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65–0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06–1.34); for rs41295061: 0.03, 0.77 (0.60–0.98)); showed a trend for association of the IL2/IL21 rs6822844 (P_M–H=0.07, OR_M–H (95% CI)=0.86 (0.73–1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation.     

RET polymorphisms might be the risk factors for thyroid cancer

Aims: The purpose of the study is to investigate the relationship between rs1799939, rs1800858 and rs74799832 polymorphisms of RET with thyroid cancer (TC) susceptibility. Methods: Genotypes distribution of control groups were tested by Hardy-Weinberg equilibrium (HWE). Rs1799939, rs1800858 and rs74799832 polymorphisms of RET were researched in 135 patients with TC and 135 healthy people using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the association between RET polymorphisms and the risk of TC by Chi-squared test. Results: Genotypes frequencies of the control group were consistent with HWE. The frequency of genotype AA and allele A in rs1799939 were significantly higher in patients with TC than controls (OR=3.768, P=0.046; OR=1.695, P=0.035). Genotype GG and allele G of rs1800858 remarkably increased the risk of TC (OR=2.149, P=0.039; OR=1.45, P=0.039). Moreover, CC genotype and C allele in rs74799832 polymorphism was related with TC susceptibility. (OR=2.28, P=0.049; OR=1.566, P=0.049). Conclusion: In present result, RET rs1799939, rs1800858 and rs74799832 polymorphisms might be the risk factors for TC.     

Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's disease from mainland China

Recently, 3 rare coding variants significantly associated with Alzheimer's disease (AD) risk have been identified in western populations using whole exome sequencing method, including p.R47H in TREM2, p.V232M in PLD3, and p.T835M in UNC5C. To examine whether these variants are genetic risk factors in patients with AD from mainland China, we sequenced exon 2 of TREM2, exon 9 of PLD3, and exon 15 of UNC5C in Chinese Han population including 360 patients with AD and 400 control individuals. As a result, none of these 3 variants were identified in all subjects, however, 1 novel variant (p.A130V) in TREM2 and 4 novel variants (p.Q860H, p.T837K, p.S843G, and p.V836V) in UNC5C were detected in unrelated patients with late-onset AD. These findings suggest the 3 rare coding variants might not play an important role in AD risk in mainland China.     

Renal cell carcinoma risk is associated with the interactions of APOE,VHL and MTHFR gene polymorphisms

Objective: The study was designed to explore the association of renal cell carcinoma (RCC) with VHL (rs779805), MTHFR (rs1801133) and APOE (rs8106822 and rs405509) polymorphisms, investigate the interactions among the single nucleotide polymorphisms (SNPs), and explore roles of the interactions in the pathogenesis of RCC in Chinese Han population. Methods: 81 RCC patients and 80 healthy controls were included in the study. Polymerase chain reaction (PCR) and direct sequencing methods were used in the analysis on the genotypes of APOE, VHL and MTHFR gene polymorphisms. Multifactor dimensionality reduction (MDR) method was adopted to conduct gene-gene interaction analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to evaluate the correlation between gene-gene interactions and RCC risk. Results: Significant correlations were found between RCC risk and 3 SNPs (rs8106822, rs779805 and rs1801133). Genotype AA and allele A of APOE rs8106822 were significantly associated with RCC susceptibility (OR=2.65, 95% CI=1.05-6.69). Meanwhile, we found that the frequencies of genotype GG and allele G were much higher in case group, compared with controls (P<0.05 for both) and they appeared to be risk factors for RCC (OR=2.90, 95% CI=1.22-6.87; OR=1.78, 95% CI=1.14-2.27). While, allele T of MTHFR rs1801133 could decrease the risk of RCC (OR=0.62, 95% CI=0.40-0.97). MDR analysis showed that gene-gene interactions among APOE, VHL and MTHFR SNPs were closely related with RCC susceptibility. Conclusion: APOE, VHL and MTHFR gene polymorphisms were related to the risk of RCC. The interactions among APOE, VHL and MTHFR genes could increase the risk of RCC.     

Lack of association between rs3807989 in cav1 and atrial fibrillation

Background: A novel gene Caveolin-1(CAV1) was identified to be susceptibility to PR interval and also associated with atrial fibrillation (AF) in two Genome wide associations studies (GWAS) studies in European ancestry. The purpose of this study was to determine the association of the SNPs in CAV1 gene of rs3807989 with AF in Chinese Han patients. Methods and results: We attempted a replication in a cohort of 839 Chinese AF patients and 1215 healthy controls using melting temperature shift allele-specific genotyping analysis. One SNP in CAV1 (rs3807989) was genotyped. The final study cohort consisted of 839 AF patients and 1215 healthy controls. No significant association was detected between rs3807989 and AF in a Chinese Han population (allelic P-adj = 0.828 with OR = 1.02; genotypic P-adj = 0.815, 0.405, 0.760 with a dominant model, recessive model, and additive model). After logistic regression with multiple covariates, the association remained non-significant with adjusted P value 0.828. When the AF cases were further divided into lone AF (31.5%) and other types of AF (68.5%), no significant association was found between rs3807989 and lone AF (P-adj = 0.929 with OR = 0.990) and other types of AF (P-adj = 0.597 with OR = 1.060). Conclusion: The SNP rs3807989 in CAV1 gene is not associated with AF or lone AF in our studies, which suggests that the SNP rs3807989 in CAV1 may not be a risk factor for AF in Chinese Han population.     

Tankyrase 1 polymorphism associated with an increased risk in developing non-small cell lung cancer in a Chinese population: a proof-of-principle study

Objectives: Tankyrase 1 (TNKS1), a poly (ADP-ribose) polymerase, regulates telomere length and apoptosis in cells, overexpression of which occurred in non-small cell lung cancer (NSCLC). This study investigated TNKS1 single-nucleotide polymorphisms (SNPs) for association with a risk in NSCLC development in a Chinese population. Methods: NSCLC cases and healthy controls of 500 each were recruited for genotyping of 24 TNKS1 SNPs. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Haploview software was to analyze association between haplotypes and NSCLC risk. Results: TNKS1 rs6601328 A allele was associated with a lower risk in developing NSCLC and adenocarcinoma (ADC) (OR=0.71; 95% CI, 0.51-0.99 and OR=0.70; 95% CI, 0.50-0.99), whereas TNKS1 rs11991621 C allele (OR=1.44; 95% CI, 1.03-2.03), rs11991621 C/C (OR=1.44, 95% CI, 1.03-2.35; P=0.03), and rs10503380 G/G (OR= 1.56, 95% CI, 1.09-2.50, P=0.02) were associated with a higher risk in developing NSCLC or ADC in females and rs6601328 A/A major allele (OR=1.39; 95% CI, 1.00-1.92; P=0.047) and rs7015700 G/G (OR= 1.51, 95% CI, 1.04-2.21) was associated with an increased NSCLC or ADC risk in males but a reduced NSCLC risk (OR=0.63; 95% CI, 0.42-0.96) and ADC risk (OR=0.64; 95% CI, 0.42-0.97) in females. Haploview showed that there were three Haplotype Blocks associated with NSCLC risk. However, TNKS1 rs12541709 C/C was associated with protective effect against ADC (OR=0.75; 95% CI, 0.56-0.99; P=0.04) in this Chinese population. Conclusion: TNKS1 SNPs (rs11991621 rs10503380, and rs7015700) were associated with NSCLC risk, whereas rs6601328 and rs12541709 inversely associated with NSCLC or ADC risk in this Chinese population.     

Lack of association between CALHM1 p.P86L variation and Alzheimer's disease in the Han Chinese population

In recent years, several studies have reported calcium homeostasis modulator 1 (CALHM1) was a potential gene related to Alzheimer's disease (AD) susceptibility. However, whether CALHM1 p.P86L variation (rs2986017), a risk factor for AD is still controversial. Two independent studies have been performed in the Chinese population and the conclusions have not reached an agreement. In the present study, we performed a replication case–control study in 1301 Chinese subjects including 452 sporadic AD patients and 849 unrelated age and gender-matched controls, to determine whether this variation is a risk factor for AD in the Han Chinese population. We failed to replicate the positive association between the CALHM1 p.P86L variation and AD. In addition, we also examined p.P86L variation in a meta-analysis of 5 independent studies performed in Chinese and other Asian populations and negative association was found in total 2328 AD patients and 2865 controls. Our study suggests that CALHM1 p.P86L variation may not be an AD susceptibility factor in the Han Chinese population.     

Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population

We performed case-control studies using 2 Canadian cohorts to examine the role of 10 promising Alzheimer's disease (AD) loci identified in recent genomewide association studies. Patients age 65 years and older diagnosed with AD at baseline (prevalent cases) or who developed AD during follow-up assessments (incident cases) were compared with control subjects with no cognitive impairment. 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. The incident case study comparing patients who developed AD during longitudinal observation (n = 152) with participants with no cognitive impairment found that rs2075650 (TOMM40) and rs3865444 (CD33) influence the risk of developing AD in this population. In addition, pooled analysis of our AD patients confirmed that CR1, TOMM40, BIN1, and CD33 contribute to late-onset AD susceptibility, in addition to apolipoprotein E.     

The rs75932628 and rs2234253 polymorphisms of the TREM2 gene were associated with susceptibility to frontotemporal lobar degeneration in Caucasian populations

Polymorphisms of the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been reported to be potentially associated with the risks of developing frontotemporal lobar degeneration (FTLD), with inconsistent conclusions. This study aims to comprehensively investigate the potential role of TREM2 variants in FTLD risks via a meta‐analysis. We included a total of eight eligible articles. For TREM2 rs75932628, we observed a significantly increased FTLD risk in the models of T vs. C [Association Test, odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.43～4.14, P = 0.001], CT vs. CC (OR = 2.27, 95% CI = 1.39～3.71, P = 0.001), CT + TT vs. CC (OR = 2.27, 95% CI = 1.38～3.71, P = 0.001), and Carrier T vs. C (OR = 2.26, 95% CI = 1.38～3.69, P = 0.001). Similarly, we observed positive results for TREM2 rs2234253 in all of the genetic models (all OR > 1, P = 0.030). Nevertheless, we did not observe any statistical difference between the case and control groups in the pooled analyses of TREM2 rs142232675 and rs143332484 (all P > 0.05). Our findings identified the rs75932628 and rs2234253 polymorphisms of the TREM2 gene as risk factors for FTLD in Caucasian populations.