Causal Association Between Allergic Diseases and Dementia: Evidence from Multivariate Mendelian Randomization Study

Article type: Research Article

Authors: Wang, YuanYing^{a; 1} | Wang, ShiHao^{b; 1} | Wu, JiaXin^{a; 1} | Liu, XinLian^{c; *} | Zhang, LuShun^{c; *}

Affiliations: [a] Graduate school, Chengdu Medical College, Chengdu, China | [b] School of Biological Science and Technology, Chengdu Medical College, Chengdu, China | [c] Department of Neurobiology, Department of Pathology and Pathophysiology, Development and Regeneration Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China

Correspondence: [*] XinLian Liu, Department of Neurobiology, Department of Pathology and Pathophysiology, Development and Regeneration Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, 610500, China. E-mail: 504080342@qq.com and LuShun Zhang, Department of Neurobiology, Department of Pathology and Pathophysiology, Development and Regeneration Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, 610500, China. Tel.: +86 17318920553; E-mail: zhangls2012@cmc.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: Background:The link between allergic diseases and dementia remains controversial, and the genetic causality of this link is unclear. Objective:This study investigated the causal relationship between allergic diseases and dementia using univariate and multivariate Mendelian randomization (MR) methods. Methods:We selected genome-wide association studies including 66,645 patients with allergic diseases and 12,281 patients with dementia, with statistical datasets derived from the FinnGen Consortium of European origin. After a rigorous screening process for single nucleotide polymorphisms to eliminate confounding effects, MR estimation was performed mainly using the inverse variance weighting method and the MR-Egger method. Sensitivity analyses were performed using Cochran’s Q test, MR-PRESSO test, MR Pleiotropy residuals and leave-one-out analysis. Results:Univariate and multivariate MR together demonstrated a causal relationship between atopic dermatitis and reduced vascular dementia (VaD) risk (OR = 0.89, 95% CI: 0.81–0.99, p = 0.031; OR = 0.85, 95% CI: 0.76–0.95, p = 0.003). MVMR confirmed asthma was associated with a reduction in the risk of Alzheimer’s disease (AD) (OR = 0.82, 95% CI: 0.71–0.94, p = 0.005) and may be associated with a reduction in the risk of VaD (OR = 0.80, 95% CI: 0.65–0.99, p = 0.042); allergic rhinitis may be causally associated with an increased risk of AD (OR = 1.16, 95% CI: 1.00–1.35, p = 0.046) and VaD (OR = 1.29, 95% CI: 1.03–1.62, p = 0.027). In sensitivity analyses, these findings were reliable. Conclusions:MR methods have only demonstrated that allergic rhinitis dementia is associated with an increased risk of developing dementia. Previously observed associations between other allergic diseases and dementia may be influenced by comorbidities and confounding factors rather than causality.

Keywords: Alzheimer’s disease, allergic rhinitis, asthma, atopic dermatitis, dementia, Mendelian randomization

DOI: 10.3233/JAD-231091

Journal: Journal of Alzheimer's Disease, vol. 98, no. 2, pp. 505-517, 2024