Authors
Xiaoyu Zhang
Qiuyue Tian
Di Liu
Tao Geng
Xizhu Xu
Siqi Ge
Deqiang Zheng
Lijuan Wu
Manshu Song
Haifeng Hou
Wei Wang, Edith Cowan UniversityFollow
Youxin Wang
Document Type
Journal Article
Publication Title
Translational Psychiatry
Publisher
Nature
School
School of Medical and Health Sciences
RAS ID
31618
Funders
The study was supported by grants from the National Key R&D Program of China (2017YFE0118800)—European Commission Horizon 2020 (779238-PRODEMOS), the National Natural Science Foundation of China (81872682 and 81773527), and the China-Australian Collaborative Grant (NSFC 81561128020-NHMRC APP1112767).
Abstract
Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58–0.84; P < 0.01), whereas carriers of ε4 allele were of increased risk of AD (OR = 3.62; 95% CI: 3.03–4.32; P < 0.05), compared to these of ε3 allele. Circulating TC was significantly reduced in carriers of ε2 allele (WMD = − 0.29 mmol/L; 95% CI: −0.54 to −0.03; P < 0.05) and increased in carriers of ε4 allele (WMD = 0.42 mmol/l; 95% CI: 0.001–0.84; P < 0.05). In addition, carriers of ε4 allele had reduction in circulating HDL-C (WMD = − 0.04 mmol/L; 95% CI: − 0.07 to −0.001; P < 0.05). In comparing allele ε2 with ε3, the predicted OR of having AD for 1 mg/dL increment in circulating TC was 0.97 (95% CI: 0.86–0.98; P < 0.05). Comparing allele ε4 with ε3, the predicted OR for a 1 mg/dL increment in TC was 1.08 (95% CI: 1.05–17.58; P < 0.05), and reduction in HDL-C was 2.30 (95% CI: 1.51–43.99; P < 0.05). Our findings demonstrate that high circulating TC and reduced HDL-C levels might be potential risk factors of the development of AD.
DOI
10.1038/s41398-020-0822-x
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Zhang, X., Tian, Q., Liu, D., Geng, T., Xu, X., Ge, S., ... & Wang, W. (2020). Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis. Translational Psychiatry, 10(1), 1-8. https://doi.org/10.1038/s41398-020-0822-x