Dataset Information

Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function.

ABSTRACT:

Background

There is considerable evidence suggesting a role of neuroinflammation in the pathogenesis of Alzheimer's disease. Establishing causality is challenging due to bias from reverse causation and residual confounding.

Methods

We used two-sample MR to explore causal effects of circulating cytokine concentrations on Alzheimer's disease risk and cognitive function. We employed genetic variants from the largest publicly available genome-wide association studies (GWASs) of cytokine concentrations (N = 8,293), Alzheimer's disease (71,880 cases/383,378 controls), prospective memory (N = 152,605 to 462,302), reaction time (N = 454,157 to 459,523) and fluid intelligence (N = 149,051).

Results

Evidence suggest that 1 standard deviation (SD) increase in levels of CTACK (CCL27) (OR = 1.09 95%CI: 1.01 to 1.19, p = 0.03) increased risk of Alzheimer's disease. There was weak evidence of a causal effect of MIP-1b (CCL4) (OR = 1.04 95% CI: 0.99 to 1.09, p = 0.08), Eotaxin (OR = 1.08 95% CI: 0.99 to 1.17, p = 0.10), GROa (CXCL1) (OR = 1.04 95% CI: 0.99 to 1.10, p = 0.15), MIG (CXCL9) (OR = 1.17 95% CI: 0.97 to 1.41, p = 0.10), IL-8 (Wald ratio: OR = 1.21 95% CI: 0.97 to 1.51, p = 0.09) and IL-2 (Wald Ratio: OR = 1.21 95% CI: 0.94 to 1.56, p = 0.14) on Alzheimer's disease risk. A 1 SD increase in concentration of Eotaxin (IVW: OR = 1.05 95% CI: 0.98 to 1.13, p = 0.14), IL-8 (OR = 1.21 95% CI: 1.07 to 1.37, p = 0.003) and MCP1 (OR = 1.07 95% CI: 1.03 to 1.13, p = 0.003) were associated with lower fluid intelligence, and IL-4 (OR = 0.86 95%CI: 0.79 to 0.98, p = 0.02) with higher.

Conclusions

Our findings suggest a causal role of cytokines in the pathogenesis of Alzheimer's disease and fluid intelligence.

SUBMITTER: Pagoni P

PROVIDER: S-EPMC10391322 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function.

Pagoni Panagiota P Korologou-Linden Roxanna S RS Howe Laura D LD Davey Smith George G Ben-Shlomo Yoav Y Stergiakouli Evie E Anderson Emma L EL

Brain, behavior, and immunity 20220514

<h4>Background</h4>There is considerable evidence suggesting a role of neuroinflammation in the pathogenesis of Alzheimer's disease. Establishing causality is challenging due to bias from reverse causation and residual confounding.<h4>Methods</h4>We used two-sample MR to explore causal effects of circulating cytokine concentrations on Alzheimer's disease risk and cognitive function. We employed genetic variants from the largest publicly available genome-wide association studies (GWASs) of cytoki ...[more]

PMID: 35580794

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Dataset Information

Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function.

Background

Methods

Results

Conclusions

Publications

Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function.

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