TY - JOUR
T1 - Genome-wide association study of serum magnesium in type 2 diabetes
AU - Oost, Lynette J.
AU - Slieker, Roderick C.
AU - Blom, Marieke T.
AU - ’t Hart, Leen M.
AU - Hoenderop, Joost G. J.
AU - Beulens, Joline W. J.
AU - de Baaij, Jeroen H. F.
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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 in TAF3 (p = 2.9 × 10−9) in people with type 2 diabetes. In skeletal muscle, loci located in TAF3 demonstrate an eQTL link to ATP5F1C, a gene that is involved in the formation of Mg2+-ATP. Serum Mg2+ levels were associated with MUC1/TRIM46 (p = 2.9 × 10−7), SHROOM3 (p = 4.0 × 10−7), and SLC22A7 (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 identified MUC1/TRIM46 (P meta = 6.9 × 10−29, P Q = 0.81) and SHROOM3 (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 of TAF3, MUC1/TRIM46, SHROOM3, and SLC22A7 in type 2 diabetes.
AB - 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 in TAF3 (p = 2.9 × 10−9) in people with type 2 diabetes. In skeletal muscle, loci located in TAF3 demonstrate an eQTL link to ATP5F1C, a gene that is involved in the formation of Mg2+-ATP. Serum Mg2+ levels were associated with MUC1/TRIM46 (p = 2.9 × 10−7), SHROOM3 (p = 4.0 × 10−7), and SLC22A7 (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 identified MUC1/TRIM46 (P meta = 6.9 × 10−29, P Q = 0.81) and SHROOM3 (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 of TAF3, MUC1/TRIM46, SHROOM3, and SLC22A7 in type 2 diabetes.
KW - GWAS
KW - Hypomagnesemia
KW - Mg
KW - Single nucleotide polymorphism
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85183358384&partnerID=8YFLogxK
U2 - 10.1186/s12263-024-00738-5
DO - 10.1186/s12263-024-00738-5
M3 - Article
C2 - 38279093
SN - 1555-8932
VL - 19
JO - Genes & nutrition
JF - Genes & nutrition
IS - 1
M1 - 2
ER -