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Meta-Analysis
. 2020 May 12;10(1):145.
doi: 10.1038/s41398-020-0822-x.

Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis

Xiaoyu Zhang  1 , Qiuyue Tian  1 , Di Liu  1 , Tao Geng  2 , Xizhu Xu  3 , Siqi Ge  4 , Deqiang Zheng  1 , Lijuan Wu  1 , Manshu Song  1 , Haifeng Hou  3 , Wei Wang  5 , Youxin Wang  6
Affiliations
Meta-Analysis

Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis

Xiaoyu Zhang et al. Transl Psychiatry. .

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Overall comparisons of ApoE gene ε2 versus ε3 in association with dementia risk.
Forest plots of the dementia risk associated with the ApoE gene ε2/ε3/ε4 alleles for ε2 vs. ε3 in all study populations.
Fig. 2
Fig. 2. Overall comparisons of ApoE gene ε4 versus ε3 in association with dementia risk.
Forest plots of the dementia risk associated with the ApoE gene ε2/ε3/ε4 alleles for ε4 vs. ε3 in all study populations.
Fig. 3
Fig. 3. Overall circulating cholesterol levels for the comparisons of ApoE gene ε2 versus ε3.
Forest plots of circulating cholesterol levels associated with the ApoE gene ε2/ε3/ε4 alleles for ε2 vs. ε3 from the available studies.
Fig. 4
Fig. 4. Overall circulating cholesterol levels for the comparisons of ApoE gene ε4 versus ε3.
Forest plots of circulating cholesterol levels associated with the ApoE gene ε2/ε3/ε4 alleles for ε4 vs. ε3 from the available studies.
See this image and copyright information in PMC

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