Analyzing 74,248 Samples Confirms the Association Between CLU rs11136000 Polymorphism and Alzheimer’s Disease in Caucasian But Not Chinese population

Abstract

Clusterin (CLU) is considered one of the most important roles for pathogenesis of Alzheimer’s Disease (AD). The early genome-wide association studies (GWAS) identified the CLU rs11136000 polymorphism is significantly associated with AD in Caucasian. However, the subsequent studies are unable to replicate these findings in different populations. Although two independent meta-analyses show evidence to support significant association in Asian and Caucasian populations by integrating the data from 18 and 25 related GWAS studies, respectively, many of the following 18 studies also reported the inconsistent results. Moreover, there are six missed and a misclassified GWAS studies in the two meta-analyses. Therefore, we suspected that the small-scale and incompletion or heterogeneity of the samples maybe lead to different results of these studies. In this study, large-scale samples from 50 related GWAS studies (28,464 AD cases and 45,784 controls) were selected afresh from seven authoritative sources to reevaluate the effect of rs11136000 polymorphism to AD risk. Similarly, we identified that the minor allele variant of rs11136000 significantly decrease AD risk in Caucasian ethnicity using the allele, dominant and recessive model. Different from the results of the previous studies, however, the results showed a negligible or no association in Asian and Chinese populations. Collectively, our analysis suggests that, for Asian and Chinese populations, the variant of rs11136000 may be irrelevant to AD risk. We believe that these findings can help to improve the understanding of the AD’s pathogenesis.

Integrating the Ribonucleic Acid Sequencing Data From Various Studies for Exploring the Multiple Sclerosis-Related Long Noncoding Ribonucleic Acids and Their Functions

“…First, we calculated the two parameters, I 2 and P value, to measure the lcnRNA expression heterogeneity by the Cochran’s Q Statistics, which is based on a chi-square test with k − 1 degrees of freedom ( k equals to the number of studies used for the meta-analysis). According to the previous studies, the heterogeneity was considered as statistically significant when I 2 > 50% and P < 0.01 (Han et al, 2015; Li et al, 2016; Liu et al, 2017; Han et al, 2018a; Xue et al, 2018). Then, the meta-analysis was performed for each of these lncRNAs based on their count values.…”

Secreted Chaperones in Neurodegeneration

“…After APOE and BIN1 , CLU is the third largest genetic risk factor for late onset AD. Multiple GWAS ( Harold et al, 2009 ; Lambert et al, 2009 ) and meta-analyses ( Liu et al, 2014 ; Zhu et al, 2018 ) have confirmed a strong correlation of the rs11136000T allele with decreased AD risk in Caucasian populations; however, the evidence for this genetic link is weaker in other ethnic groups ( Han et al, 2018 ). This protective allele is associated with increased clusterin expression ( Ling et al, 2012 ).…”

Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine

“…Using multiple independent data sets of individuals with MCI, variants in the CLU gene have emerged as players in the risk of the conversion of patients from MCI to AD (Lacour et al, 2017). Variants in the CLU gene have been identified as potential risk factors in late-onset AD, specifically in Caucasian populations (Han, Qu, Zhao, & Zou, 2018;Lu et al, 2014;Nordestgaard et al, 2018;Szymanski, Wang, Bassett, & Avramopoulos, 2011;Zhang et al, 2016).…”