Polygenic Analysis of Late-Onset Alzheimer's Disease from Mainland China

Bin Jiao; Xiaoyan Liu; Lin Zhou; Maggie Haitian Wang; Yafang Zhou; Tingting Xiao; Weiwei Zhang; Rui Sun; Mary Miu Yee Waye; Beisha Tang; Lu Shen

doi:10.1371/journal.pone.0144898

Polygenic Analysis of Late-Onset Alzheimer's Disease from Mainland China

PLoS One. 2015 Dec 17;10(12):e0144898. doi: 10.1371/journal.pone.0144898. eCollection 2015.

Authors

Bin Jiao¹, Xiaoyan Liu¹, Lin Zhou^{1

2}, Maggie Haitian Wang³, Yafang Zhou^{1

2}, Tingting Xiao¹, Weiwei Zhang¹, Rui Sun³, Mary Miu Yee Waye⁴, Beisha Tang^{1

5

2}, Lu Shen^{1

5

2}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
² Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
³ Division of Biostatistics, School of Public Health and Primary Care, the Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region.
⁴ School of Biomedical Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region.
⁵ State Key Laboratory of Medical Genetics, Changsha, China.

Abstract

Recently, a number of single nucleotide polymorphisms (SNPs) were identified to be associated with late-onset Alzheimer disease (LOAD) through genome-wide association study data. Identification of SNP-SNP interaction played an important role in better understanding genetic basis of LOAD. In this study, fifty-eight SNPs were screened in a cohort of 229 LOAD cases and 318 controls from mainland China, and their interaction was evaluated by a series of analysis methods. Seven risk SNPs and six protective SNPs were identified to be associated with LOAD. Risk SNPs included rs9331888 (CLU), rs6691117 (CR1), rs4938933 (MS4A), rs9349407 (CD2AP), rs1160985 (TOMM40), rs4945261 (GAB2) and rs5984894 (PCDH11X); Protective SNPs consisted of rs744373 (BIN1), rs1562990 (MS4A), rs597668 (EXOC3L2), rs9271192 (HLA-DRB5/DRB1), rs157581 and rs11556505 (TOMM40). Among positive SNPs presented above, we found the interaction between rs4938933 (risk) and rs1562990 (protective) in MS4A weakened their each effect for LOAD; for three significant SNPs in TOMM40, their cumulative interaction induced the two protective SNPs effects lost and made the risk SNP effect aggravate for LOAD. Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970-rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk. In a word, our study indicates that SNP-SNP interaction existed in the same gene or cross different genes, which could weaken or aggravate their initial single effects for LOAD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age of Onset
Aged
Alzheimer Disease / epidemiology
Alzheimer Disease / genetics*
Apolipoproteins E / genetics
China / epidemiology
Female
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Humans
Male
Polymorphism, Single Nucleotide / genetics*

Substances

Apolipoproteins E

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81471295, sponsored by LS, http://npd.nsfc.gov.cn/); the Natural Science Foundation of Hunan Province (No.14jj7011, sponsored by LZ, http://www.hnst.gov.cn/zxgz/zkjj/); Hunan Provincial Innovation Foundation For Postgraduate (No. CX2014B113, sponsored by BJ, http://wenku.baidu.com/link?url=J1uokswv7ZGiIQboCUWwU8GV9hJTic2aGOP2S3rTW9uT3_fGaFF1neXBII2-l9xLhZFMOBhqD-kBAT3hSMF91WE2bi2OyKU_shtFYDKbtJq).