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Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese.
Mol Neurobiol. 2017 01; 54(1):308-318.MN

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) have overlapping pathological mechanisms and genetic background, suggesting it would be meaningful to replicate PD-related genetic variants in AD population to identify new loci of AD. Here, in order to discover potential AD-related loci, we investigated the association between late-onset AD (LOAD) susceptibility and nine single-nucleotide polymorphisms (SNPs) (rs11724635 of BST1, rs12637471 of MCCC1, rs15553999 of TMEM229, rs17649553 of MAPT, rs34311866 of TMEM175-GAK-DGKQ, rs356182 of SNCA, rs6430538 of ACMSD-TMEM163, rs76904798 of LRRK2 and rs823118 of RAB7L1-NUCKS1) which were reported to have genome-wide significant associations with PD risk in a recent Genome Wide Association Study performed among white population. We included 2350 samples comprising with 992 sporadic LOAD patients and 1358 gender- and age-matched control subjects who were unrelated northern Han Chinese residents. Finally, among these included genetic variants, only rs76904798 of LRRK2 was proved to significantly reduce LOAD risk in a multivariate analysis in a dominant model after adjusting for age, sex, and apolipoprotein E (APOE) ε4 status (OR = 0.616; 95 % CI 0.446-0.849; Bonferroni corrected P = 0.027). In addition, when these data were stratified by APOE ε4 status, rs76904798 was still evident among subjects without APOE ε4 allele. Our results first time indicated rs76904798 of LRRK2 is also a common risk genetic variant for LOAD susceptibility in a northern Han Chinese people.

Authors+Show Affiliations

Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China. dr.tanlan@163.com. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. dr.tanlan@163.com. Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China. dr.tanlan@163.com.Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China. jintai.yu@ucsf.edu. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. jintai.yu@ucsf.edu. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. jintai.yu@ucsf.edu.

Pub Type(s)

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

Language

eng

PubMed ID

26738859

Citation

Zhu, Xi-Chen, et al. "Association of Parkinson's Disease GWAS-Linked Loci With Alzheimer's Disease in Han Chinese." Molecular Neurobiology, vol. 54, no. 1, 2017, pp. 308-318.
Zhu XC, Cao L, Tan MS, et al. Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese. Mol Neurobiol. 2017;54(1):308-318.
Zhu, X. C., Cao, L., Tan, M. S., Jiang, T., Wang, H. F., Lu, H., Tan, C. C., Zhang, W., Tan, L., & Yu, J. T. (2017). Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese. Molecular Neurobiology, 54(1), 308-318. https://doi.org/10.1007/s12035-015-9649-5
Zhu XC, et al. Association of Parkinson's Disease GWAS-Linked Loci With Alzheimer's Disease in Han Chinese. Mol Neurobiol. 2017;54(1):308-318. PubMed PMID: 26738859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese. AU - Zhu,Xi-Chen, AU - Cao,Lei, AU - Tan,Meng-Shan, AU - Jiang,Teng, AU - Wang,Hui-Fu, AU - Lu,Huan, AU - Tan,Chen-Chen, AU - Zhang,Wei, AU - Tan,Lan, AU - Yu,Jin-Tai, Y1 - 2016/01/06/ PY - 2015/10/01/received PY - 2015/12/17/accepted PY - 2016/1/8/pubmed PY - 2018/2/10/medline PY - 2016/1/8/entrez KW - Alzheimer’s disease KW - Association study KW - Parkinson’s disease KW - Polymorphisms KW - Susceptibility SP - 308 EP - 318 JF - Molecular neurobiology JO - Mol Neurobiol VL - 54 IS - 1 N2 - Alzheimer's disease (AD) and Parkinson's disease (PD) have overlapping pathological mechanisms and genetic background, suggesting it would be meaningful to replicate PD-related genetic variants in AD population to identify new loci of AD. Here, in order to discover potential AD-related loci, we investigated the association between late-onset AD (LOAD) susceptibility and nine single-nucleotide polymorphisms (SNPs) (rs11724635 of BST1, rs12637471 of MCCC1, rs15553999 of TMEM229, rs17649553 of MAPT, rs34311866 of TMEM175-GAK-DGKQ, rs356182 of SNCA, rs6430538 of ACMSD-TMEM163, rs76904798 of LRRK2 and rs823118 of RAB7L1-NUCKS1) which were reported to have genome-wide significant associations with PD risk in a recent Genome Wide Association Study performed among white population. We included 2350 samples comprising with 992 sporadic LOAD patients and 1358 gender- and age-matched control subjects who were unrelated northern Han Chinese residents. Finally, among these included genetic variants, only rs76904798 of LRRK2 was proved to significantly reduce LOAD risk in a multivariate analysis in a dominant model after adjusting for age, sex, and apolipoprotein E (APOE) ε4 status (OR = 0.616; 95 % CI 0.446-0.849; Bonferroni corrected P = 0.027). In addition, when these data were stratified by APOE ε4 status, rs76904798 was still evident among subjects without APOE ε4 allele. Our results first time indicated rs76904798 of LRRK2 is also a common risk genetic variant for LOAD susceptibility in a northern Han Chinese people. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/26738859/Association_of_Parkinson's_Disease_GWAS_Linked_Loci_with_Alzheimer's_Disease_in_Han_Chinese_ L2 - https://dx.doi.org/10.1007/s12035-015-9649-5 DB - PRIME DP - Unbound Medicine ER -