Association of Parkinson’s Disease GWAS-Linked Loci with Alzheimer’s Disease in Han Chinese

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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81571245, 81501103), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, and the Innovation Project for Postgraduates of Jiangsu province (to XCZ (KYLX15_0958)).

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Correspondence to Lan Tan or Jin-Tai Yu.

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We obtained informed consents from each subject or a guardian, and this study protocol was approved by the institutional ethics committees of Qingdao Municipal Hospital.

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The authors declare that they have no competing interests.

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Xi-Chen Zhu and Lei Cao contributed equally to this work.

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The details of the primer sequences used for the polymerase chain reaction–ligase detection reaction. (DOC 56 kb)

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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 54, 308–318 (2017). https://doi.org/10.1007/s12035-015-9649-5

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Keywords

  • Alzheimer’s disease
  • Parkinson’s disease
  • Polymorphisms
  • Susceptibility
  • Association study