Analyzing 54,936 Samples Supports the Association Between CD2AP Rs9349407 Polymorphism and Alzheimer's Disease Susceptibility

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2014 Aug 6

PMID 25092125

Citations 31

Authors

Hongyuan Chen

Guihua Wu

Yongshuai Jiang

Rennan Feng

Mingzhi Liao

Liangcai Zhang

Guoda Ma

Zugen Chen

Bin Zhao

Keshen Li

Chunjiang Yu

Guiyou Liu

Affiliations

Soon will be listed here.

Abstract

The CD2-associated protein (CD2AP) rs9349407 polymorphism was first identified to be significantly associated with Alzheimer's disease (AD) in European ancestry by genome-wide association studies (GWAS). However, the following studies reported no association in Chinese, Japanese, African-American, Canadian, and European populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs9349407 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from 15 previous studies (N = 54,936; 23,777 cases and 31,159 controls) by searching the PubMed, AlzGene, and Google Scholar databases. Using an additive genetic model, we did not identify a significant heterogeneity among the 15 studies. Using meta-analysis, we observed a significant association between the rs9349407 polymorphism and AD with P = 8.78E-07, odds ratio (OR) = 1.08, 95% confidence interval (CI) 1.05-1.12. To our knowledge, this is the first meta-analysis to investigate the association between rs9349407 polymorphism and AD in East Asian, American, Canadian, and European populations. Our analysis further supports previous findings that the CD2AP rs9349407 polymorphism contributes to AD susceptibility. We believe that our findings will be very useful for future genetic studies on AD.

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References

Omoumi A, Fok A, Greenwood T, Sadovnick A, Feldman H, Hsiung G . Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population. Neurobiol Aging. 2013; 35(4):936.e5-12. DOI: 10.1016/j.neurobiolaging.2013.09.025. View

Naj A, Jun G, Beecham G, Wang L, Vardarajan B, Buros J . Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet. 2011; 43(5):436-41. PMC: 3090745. DOI: 10.1038/ng.801. View

Hollingworth P, Harold D, Sims R, Gerrish A, Lambert J, Carrasquillo M . Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat Genet. 2011; 43(5):429-35. PMC: 3084173. DOI: 10.1038/ng.803. View

Gogele M, Minelli C, Thakkinstian A, Yurkiewich A, Pattaro C, Pramstaller P . Methods for meta-analyses of genome-wide association studies: critical assessment of empirical evidence. Am J Epidemiol. 2012; 175(8):739-49. DOI: 10.1093/aje/kwr385. View

Jiang Y, Zhang R, Zheng J, Liu P, Tang G, Lv H . Meta-analysis of 125 rheumatoid arthritis-related single nucleotide polymorphisms studied in the past two decades. PLoS One. 2012; 7(12):e51571. PMC: 3519690. DOI: 10.1371/journal.pone.0051571. View

Lewis C, Knight J . Introduction to genetic association studies. Cold Spring Harb Protoc. 2012; 2012(3):297-306. DOI: 10.1101/pdb.top068163. View

Tan L, Yu J, Zhang W, Wu Z, Zhang Q, Liu Q . Association of GWAS-linked loci with late-onset Alzheimer's disease in a northern Han Chinese population. Alzheimers Dement. 2012; 9(5):546-53. DOI: 10.1016/j.jalz.2012.08.007. View

Lv H, Jiang Y, Li J, Zhang M, Shang Z, Zheng J . Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease. Mol Biol Rep. 2014; 41(3):1299-310. DOI: 10.1007/s11033-013-2975-7. View

Lambert J, Grenier-Boley B, Chouraki V, Heath S, Zelenika D, Fievet N . Implication of the immune system in Alzheimer's disease: evidence from genome-wide pathway analysis. J Alzheimers Dis. 2010; 20(4):1107-18. DOI: 10.3233/JAD-2010-100018. View

10.

Miyashita A, Koike A, Jun G, Wang L, Takahashi S, Matsubara E . SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians. PLoS One. 2013; 8(4):e58618. PMC: 3614978. DOI: 10.1371/journal.pone.0058618. View

11.

Liu G, Li F, Zhang S, Jiang Y, Ma G, Shang H . Analyzing large-scale samples confirms the association between the ABCA7 rs3764650 polymorphism and Alzheimer's disease susceptibility. Mol Neurobiol. 2014; 50(3):757-64. DOI: 10.1007/s12035-014-8670-4. View

12.

Zhang S, Zhang D, Jiang Y, Wu L, Shang H, Liu J . CLU rs2279590 polymorphism contributes to Alzheimer's disease susceptibility in Caucasian and Asian populations. J Neural Transm (Vienna). 2014; 122(3):433-9. DOI: 10.1007/s00702-014-1260-9. View

13.

Shulman J, Chen K, Keenan B, Chibnik L, Fleisher A, Thiyyagura P . Genetic susceptibility for Alzheimer disease neuritic plaque pathology. JAMA Neurol. 2013; 70(9):1150-7. PMC: 3773291. DOI: 10.1001/jamaneurol.2013.2815. View

14.

Liu G, Yao L, Liu J, Jiang Y, Ma G, Chen Z . Cardiovascular disease contributes to Alzheimer's disease: evidence from large-scale genome-wide association studies. Neurobiol Aging. 2013; 35(4):786-92. DOI: 10.1016/j.neurobiolaging.2013.10.084. View

15.

Liu G, Zhang S, Cai Z, Li Y, Cui L, Ma G . BIN1 gene rs744373 polymorphism contributes to Alzheimer's disease in East Asian population. Neurosci Lett. 2013; 544:47-51. DOI: 10.1016/j.neulet.2013.02.075. View

16.

Logue M, Schu M, Vardarajan B, Buros J, Green R, Go R . A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol. 2011; 68(12):1569-79. PMC: 3356921. DOI: 10.1001/archneurol.2011.646. View

17.

Clark M, Baudouin S . A systematic review of the quality of genetic association studies in human sepsis. Intensive Care Med. 2006; 32(11):1706-12. DOI: 10.1007/s00134-006-0327-y. View

18.

Shen N, Chen B, Jiang Y, Feng R, Liao M, Zhang L . An Updated Analysis with 85,939 Samples Confirms the Association Between CR1 rs6656401 Polymorphism and Alzheimer's Disease. Mol Neurobiol. 2014; 51(3):1017-23. DOI: 10.1007/s12035-014-8761-2. View

19.

Liu G, Zhang L, Feng R, Liao M, Jiang Y, Chen Z . Lack of association between PICALM rs3851179 polymorphism and Alzheimer's disease in Chinese population and APOEε4-negative subgroup. Neurobiol Aging. 2012; 34(4):1310.e9-10. DOI: 10.1016/j.neurobiolaging.2012.08.015. View

20.

Liu G, Wang H, Liu J, Li J, Li H, Ma G . The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations. Neuromolecular Med. 2013; 16(1):52-60. DOI: 10.1007/s12017-013-8250-1. View