The Association of Wnt Signaling Pathway Gene Variants, Blood Lipoproteins and Cognitive Function in Elderly People.

Wnt signaling is believed to play an important role in the nervous system. However, few studies have examined the association between gene variants of the Wnt signaling pathway and mild cognitive impairment (MCI). Additionally, the potential modulation of this association by blood lipoproteins remains poorly understood. We aimed to investigate these associations in the present analysis. The cross-sectional study comprised 459 participants from 17 villages in Jimo District, Qingdao, Shandong Province. A total of 46 single nucleotide polymorphisms (SNPs) in nine Wnt signaling pathway genes were included. Cognitive function was measured using Montreal Cognitive Assessment (MOCA). Polygenic risk scores (PRS) were used to summarize the effect of each gene. Ordered logistic regression and Poisson regression with robust variance were applied to examine the associations of SNPs with MCI and the dimension score of MOCA. Interaction analysis was conducted to verify the interaction with lipoproteins. A random forest classifier was used to develop a predictive model for MCI. The SNP PRKCA-rs2286674 was associated with MCI across three models. The risk of MCI increased by 31% and 2% for each unit increase of PRS of PRKCA and WNT7B respectively. Based on the multiplicative interaction model, the effects of certain PRSs on the risk of MCI were modified by blood lipoproteins. Integrating total PRS into the prediction model significantly improved the ability to predict MCI. Genetic variations in Wnt signaling pathway were associated with MCI in older adults. Interaction effects between gene variants and blood lipoproteins on MCI were observed.