期刊
FRONTIERS IN MEDICINE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2021.798334
关键词
low-density lipoprotein cholesterol; Alzheimer's disease; family history; mendelian randomization; familial Alzheimer's disease
资金
- National Key Research and Development Program of China [2017YFC1700503]
- Capital's Funds for Health Improvement and Research [2018-2-4031]
- Capital's Funds for Research and Application of Clinical Diagnosis and Treatment Technology [Z191100006619121]
This study used Mendelian randomization to explore the causal associations between LDL-C level and the risks of individual and familial Alzheimer's disease (AD). The results showed a positive association between genetically predicted LDL-C and individual, paternal, maternal, and family history of AD, suggesting that high LDL-C level may increase the risks of both individual and familial AD. Lowering LDL-C level to a reasonable range may help reduce the related risk.
Background: Previous observational studies provided conflicting results on the association between low-density lipoprotein cholesterol (LDL-C) level and the risk of Alzheimer's disease (AD).Objective: We used two-sample Mendelian randomization (MR) study to explore the causal associations between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.Methods: Summary-level genetic data for LDL-C were acquired from results of the UK Biobank GWAS. Corresponding data for paternal, maternal, and family history of AD were obtained from the NHGRI-EBI Catalog of human genome-wide association studies. Data for individual AD were obtained from the MR-Base platform. A two-sample MR study was performed to explore the causal association between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.Results: Genetically predicted LDL-C was positively associated with individual [Odds ratio (OR) = 1.509, 95% confidence interval (CI) = 1.140-1.999; P = 4.0 x 10(-3)], paternal [OR = 1.109, 95% CI = 1.053-1.168; P = 9.5 x 10(-5)], maternal [OR = 1.132, 95% CI = 1.070-1.199; P = 2.0 x 10(-5)], and family history of AD [OR = 1.124, 95% CI = 1.070-1.181; P = 3.7 x 10(-6)] in inverse variance weighted analysis. After performing weighted median and MR-Egger analysis, consistent results were observed. There was no horizontal pleiotropy in the two-sample MR analysis.Conclusions: High level of LDL-C may increase the risks of both individual and familial AD. Decreasing the LDL-C to a reasonable level may help to reduce the related risk.
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