MR-PheWAS for the causal effects of serum magnesium on multiple disease outcomes in Caucasian descent

Abstract

Magnesium is integral to many physiological processes, whereas variations in its levels, even within the normal range, can have critical implications for health. To explore the broad clinical effects of varying serum magnesium levels, we performed a two-sample Mendelian randomization and phenome-wide association study (MR-PheWAS) in the UK Biobank cohort. In total, MR-PheWAS analysis implicated a causal role of serum magnesium levels in five disease groups and six disease outcomes. In addition, our study indicated the gender-specific effects of nine disease groups/outcomes in MR estimated effects. The protein-protein interaction network demonstrated an interaction between the serum magnesium-associated gene DCDC1 and the cataract- associated gene PAX6. The present study verified several previously reported disease outcomes and identified novel potential disease outcomes for serum magnesium levels. The DCDC1 gene and the PAX6 gene may be the new targets for promoting the treatments of cataracts using magnesium intervention.

Keywords: Bioinformatics; Clinical medicine; Complex system biology; Medicine; Omics; Pathophysiology.

Graphical abstract

Figure 1

Diagram of the interactions between the serum magnesium-associated genes and the cataract-associated genes Mg^a: the top ten associated genes of serum magnesium were searched for using the GeneCards website (https://www.genecards.org/). Mg^b: the instrumental variable SNPs located genes of serum magnesium. Mg^c: the gene is the top ten genes as well as the instrumental variable SNPs located genes of serum magnesium. All confidence scores range from 0.4 to 1, while one is the highest. The darker the green line with the arrow, the higher the confidence score, indicating a stronger interaction between the two genes.