Impact of Serum Calcium Levels on Alzheimer’s Disease: A Mendelian Randomization Study

He, Yating; Zhang, Haihua; Wang, Tao; Han, Zhifa; Ni, Qing-bin; Wang, Kun; Wang, Longcai; Zhang, Yan; Hu, Yang; Jin, Shuilin; Sun, Bao-liang; Liu, Guiyou

doi:10.3233/jad-191249

Cited by 15 publications

References 58 publications

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“…However, the statistical methods could not completely exclude all confounders. It is a general challenge in current MR studies (Emdin et al, 2017;Larsson et al, 2017aLarsson et al, , 2019He et al, 2020). Hence, follow-up studies are necessary to replicate our findings.…”

Section: Discussionmentioning

confidence: 80%

“…Using the summary results of these 14 genetic variants in both serum calcium levels and IS GWAS datasets, we first conducted a pleiotropy analysis using two statistical methods including the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test (Verbanck et al, 2018). Both methods have been widely used in recent MR studies (Liu et al, 2018;Larsson et al, 2019;He et al, 2020;Wang et al, 2020). The statistical significance for evidence of pleiotropy is P < 0.05.…”

Section: Pleiotropy Analysismentioning

confidence: 99%

“…For MR analysis, we selected 11 MR methods including simple median, weighted median, penalized weighted median, IVW, penalized IVW, robust IVW, penalized robust IVW, MR-Egger, penalized MR-Egger, robust MR-Egger, and penalized robust MR-Egger (Larsson et al, 2019;He et al, 2020). IVW is a standard MR analysis method.…”

Section: Mr Analysismentioning

confidence: 99%

“…IVW is a standard MR analysis method. For multiple independent genetic variants, IVW could weigh the average of these single causal estimates using the inverse of their approximate variances as weights Larsson et al, 2019;He et al, 2020). The causal estimate from the MR-Egger is obtained using the same regression model as the weighted linear regression described above, but allowing the intercept to be estimated as part of the analysis .…”

Section: Mr Analysismentioning

confidence: 99%

“…where β is the effect size (beta coefficient) between SNP i and the serum calcium levels, MAF SNP i is the minor allele frequency for SNP i , and SD = 0.5 mg/dl (Larsson et al, 2017a;He et al, 2020). Using R 2 and other necessary information, we performed a power analysis using mRnd: Power calculations for MR 1 (Brion et al, 2013).…”

Section: Power Analysismentioning

confidence: 99%

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Integrated Genetics and Micronutrient Data to Inform the Causal Association Between Serum Calcium Levels and Ischemic Stroke

Meng

Huang

Tao

et al. 2020

Front. Cell Dev. Biol.Has correction 2020-12-18 Has erratum 2020-12-18

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There has been an increased interest for observational studies or randomized controlled trials exploring the impact of calcium intake on cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic stroke (IS). However, a direct relationship between total calcium intake and CVD has not been well established and remains controversial. Mendelian randomization (MR) studies have been performed to evaluate the causal association between serum calcium levels and CAD risk and found that increased serum calcium levels could increase the risk of CAD. However, MR analysis found no significant association between genetically higher serum calcium levels and IS as well as its subtypes. Hence, three MR studies reported inconsistent effects of serum calcium levels on CAD and IS. Here, we performed an updated MR study to investigate the association of serum calcium levels with the risk of IS using large-scale genome-wide association study (GWAS) datasets. We selected 14 independent genetic variants as the potential instrumental variables from a large-scale serum calcium GWAS dataset and extracted summary statistics corresponding to the 14 serum calcium genetic variants from the MEGASTROKE Consortium IS GWAS dataset. Interestingly, we found a significant association between serum calcium levels and IS risk using the robust inverse-variance weighted (IVW) and penalized robust IVW methods, with β = 0.243 and P = 0.002. Importantly, the MR results from the robust MR-Egger and penalized robust MR-Egger methods further supported the causal association between serum calcium levels and IS risk, with β = 0.256 and P = 0.005. Meanwhile, the estimates from other MR methods are also consistent with the above findings.

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Section: Discussionmentioning

confidence: 80%