Validating GWAS-Identified Risk Loci for Alzheimer’s Disease in Han Chinese Populations

Abstract

In recent years, genome-wide association studies (GWASs) have identified many novel susceptible genes/loci for Alzheimer's disease (AD). However, most of these studies were conducted in European and populations of European origin, and limited studies have been performed in Han Chinese. In this study, we genotyped 14 single-nucleotide polymorphisms (SNPs) in eight GWAS-reported AD risk genes in 1509 individuals comprising two independent Han Chinese case-control cohorts. Four SNPs (rs11234495, rs592297, rs676733, and rs3851179) in the PICALM gene were significantly associated with late-onset (LO)-AD in populations from Southwest China, whereas SNPs rs744373 (BIN1), rs9331942 (CLU), and rs670139 (MS4A4E) were linked to LO-AD in populations from East China. In the combined Han Chinese population, positive associations were observed between PICALM, CLU, MS4A4E genes, and LO-AD. The association between rs3851179 (PICALM), rs744373 (BIN1), and AD was further confirmed by meta-analysis of Asian populations. Our study verified the association between PICALM, BIN1, CLU, and MS4A4E variants and AD susceptibility in Han Chinese populations. We also discerned some regional differences concerning AD susceptibility SNPs.

CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer’s Disease

“…In stage 2, we recruited 345 patients (AD2), 337 healthy individuals from the general populations (PC2) and 504 healthy longevity individuals (LC, age 93 ± 2.6 years; as another control) from Southwest China. Most of these AD patients had been analyzed for other risk loci in our recent studies (Bi et al, 2015;Bi et al, 2014;Wang et al, 2014). In brief, patients were diagnosed following the DSM-IV and the NINCDS-ADRDA criteria independently by at least two senior clinicians.…”

“…The selection criteria and details for selected SNPs were described in the supplementary Methods and Table S1. APOE ε4 was determined as previously described (Bi et al, 2015;Bi et al, 2014;Wang et al, 2014).…”

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

“…The association has been further supported in other populations. For instance, variants of immune-related genes, including complement factor H [10], MS4A [11], CR1 [12], and CD33 [13] are associated with AD susceptibility in Han Chinese.…”

Genome instability in Alzheimer disease

“…Most cases of AD are sporadic AD, which include different susceptible genes/loci and the courses of the disease can be different for each individual (Wang et al, 2016), indicating that epigenetic and environmental factors play an important role in AD etiology. Many studies have shown that methylation plays an essential role in AD occurrence (Zawia et al, 2009).…”