Genome-wide association study of serum magnesium in type 2 diabetes

People with type 2 diabetes have a tenfold higher prevalence of hypomagnesemia, which is suggested to be caused by low dietary magnesium intake, medication use, and genetics. This study aims to identify the genetic loci that influence serum magnesium concentration in 3466 people with type 2 diabetes. The GWAS models were adjusted for age, sex, eGFR, and HbA1c. Associated traits were identified using publicly available data from GTEx consortium, a human kidney eQTL atlas, and the Open GWAS database. The GWAS identified a genome-wide significant locus inTAF3(p = 2.9 × 10⁻⁹) in people with type 2 diabetes. In skeletal muscle, loci located inTAF3demonstrate an eQTL link toATP5F1C, a gene that is involved in the formation of Mg²⁺-ATP. Serum Mg²⁺levels were associated withMUC1/TRIM46(p = 2.9 × 10⁻⁷), SHROOM3(p = 4.0 × 10⁻⁷), andSLC22A7(p = 1.0 × 10⁻⁶) at nominal significance, which is in combination with the eQTL data suggesting that they are possible candidates for renal failure. Several genetic loci were in agreement with previous genomic studies which identifiedMUC1/TRIM46(P_meta = 6.9 × 10⁻²⁹,P_Q = 0.81) andSHROOM3(P_meta = 2.9 × 10⁻²⁷,P_Q = 0.04) to be associated with serum Mg²⁺in the general population. In conclusion, serum magnesium concentrations are associated with genetic variability around the regions ofTAF3, MUC1/TRIM46, SHROOM3, andSLC22A7in type 2 diabetes.