Assessing the impact of novel risk loci on Alzheimer's and Parkinson's diseases in a Chinese Han cohort

Huimin Yan; Minglei Liu; Yuan Gao; Yanpeng Yuan; Xiaojing Liu; Yangyang Wang; Lanjun Li; Qingzhi Wang; Yanlin Wang; Changhe Shi; Yuming Xu; Jing Yang

doi:10.3389/fneur.2024.1326692

Assessing the impact of novel risk loci on Alzheimer's and Parkinson's diseases in a Chinese Han cohort

Front Neurol. 2024 Jan 31:15:1326692. doi: 10.3389/fneur.2024.1326692. eCollection 2024.

Authors

Huimin Yan¹, Minglei Liu¹, Yuan Gao^{1

2

3

4}, Yanpeng Yuan^{1

2

3

4}, Xiaojing Liu^{1

2

4}, Yangyang Wang^{1

2

4}, Lanjun Li^{1

2}, Qingzhi Wang¹, Yanlin Wang^{1

2

3

4}, Changhe Shi^{1

4}, Yuming Xu^{1

2

3

4}, Jing Yang^{1

2

3}

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
² NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China.
³ Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China.
⁴ Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China.

Abstract

Background: Overwhelming evidence points to that genetic factors contributing to the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Genome-Wide Association Study (GWAS) has come a long way in the last decade. So far, a large number of GWAS studies have been published on neurological diseases and many other diseases, providing us with a wealth of genetic information and unique biological insights.

Methods: Genomic DNA was extracted from both patients' and controls' peripheral blood samples utilizing the Blood Genome Extraction Kit. Single nucleotide polymorphisms (SNPs) were genotyped employing the enhanced multiple ligase detection reaction (iMLDR) technology.

Results: A case-control study was conducted, involving 211 AD patients, 508 PD patients (including 117 with dementia), and 412 healthy individuals. Age and sex stratification analysis revealed that rs871269/TNIP1 was associated with LOAD (p = 0.035), and rs5011436/TMEM106B was associated with AD in males (p = 0.044) in the genotype model. In the allele model, rs871269/TNIP1 was found to be associated with PD in the Chinese Han population (p = 0.0035, OR 0.741, 95% CI 0.559-0.983), and rs708382/GRN was identified as a risk factor for Parkinson's disease dementia (PDD) in the Chinese Han population (p = 0.004, odds ratio (OR) 0.354, 95% confidence interval (CI) 0.171-0.733). However, no significant associations with AD or PD were observed for the remaining four loci (rs113020870/AGRN, rs6891966/HAVCR2, rs2452170/NTN5, rs1761461/LILRB2) in terms of allele or genotype frequencies.

Conclusion: This study identifies rs871269/TNIP1 as a potential risk factor for both LOAD and PD, rs708382/GRN as a risk factor for PDD, and rs5011436/TMEM106B as associated with AD in males when stratified by age.

Keywords: Alzheimer’s disease; Chinese Han cohort; Parkinson’s disease; Parkinson’s disease dementia; single nucleotide polymorphisms.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China to YX (U1904207), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences to YX (2020-PT310-01), the National Natural Science Foundation of China to JY (82171434), the Excellent Youth Project of Henan Provincial Natural Science Foundation to JY (222300420070), the Henan Province Young and Middle-Aged Health Science and Technology Innovation Outstanding Youth Training Project to JY (YXKC2020031), and the Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University (QNCXTD2023016).