Research Papers: Pathology:

Genome-wide haplotype association study identify TNFRSF1A, CASP7, LRP1B, CDH1 and TG genes associated with Alzheimer’s disease in Caribbean Hispanic individuals

Zhenwei Shang, Hongchao Lv, Mingming Zhang, Lian Duan, Situo Wang, Jin Li, Guiyou Liu, Zhang Ruijie and Yongshuai Jiang _

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Oncotarget. 2015; 6:42504-42514. https://doi.org/10.18632/oncotarget.6391

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Zhenwei Shang1,*, Hongchao Lv1,*, Mingming Zhang1,*, Lian Duan1,* Situo Wang2, Jin Li1, Guiyou Liu3, Zhang Ruijie1 and Yongshuai Jiang1

1 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

2 Genetic Data Analysis Group, The Genome Science Consortium, Harbin, China

3 Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China

* Joint First Authors

Correspondence to:

Yongshuai Jiang, email:

Zhang Ruijie, email:

Keywords: Alzheimer’s disease, haplotype association analysis, Pathology Section

Received: June 29, 2015 Accepted: November 16, 2015 Published: November 25, 2015


Alzheimer’s disease (AD) is an acquired disorder of cognitive and behavioral impairment. It is considered to be caused by variety of factors, such as age, environment and genetic factors. In order to identify the genetic affect factors of AD, we carried out a bioinformatic approach which combined genome-wide haplotype-based association study with gene prioritization. The raw SNP genotypes data was downloaded from GEO database (GSE33528). It contains 615 AD patients and 560 controls of Caribbean Hispanic individuals. Firstly, we identified the linkage disequilibrium (LD) haplotype blocks and performed genome-wide haplotype association study to screen significant haplotypes that were associated with AD. Then we mapped these significant haplotypes to genes and obtained candidate genes set for AD. At last, we prioritized AD candidate genes based on their similarity with 36 known AD genes, so as to identify AD related genes. The results showed that 141 haplotypes on 134 LD blocks were significantly associated with AD (P<1E-4), and these significant haplotypes were mapped to 132 AD candidate genes. After prioritizing these candidate genes, we found seven AD related genes: APOE, APOC1, TNFRSF1A, LRP1B, CDH1, TG and CASP7. Among these genes, APOE and APOC1 are known AD risk genes. For the other five genes TNFRSF1A, CDH1, CASP7, LRP1B and TG, this is the first genetic association study which showed the significant association between these five genes and AD susceptibility in Caribbean Hispanic individuals. We believe that our findings can provide a new perspective to understand the genetic affect factors of AD.

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