Phenome-Wide Association Study of Latent Autoimmune Diabetes from a Southern Mexican Population Implicates rs7305229 with Plasmatic Anti-Glutamic Acid Decarboxylase Autoantibody (GADA) Levels

• Published in: International journal of molecular sciences Vol. 25; no. 18; p. 10154
• Main Authors: Nolasco-Rosales, Germán Alberto, Martínez-Magaña, José Jaime, Juárez-Rojop, Isela Esther, Rodríguez-Sánchez, Ester, Ruiz-Ramos, David, Villatoro-Velázquez, Jorge Ameth, Bustos-Gamiño, Marycarmen, Medina-Mora, Maria Elena, Tovilla-Zárate, Carlos Alfonso, Cruz-Castillo, Juan Daniel, Nicolini, Humberto, Genis-Mendoza, Alma Delia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.09.2024; MDPI
• Subjects: Adult; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Autoimmunity; Body mass index; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetics; fas apoptotic inhibitory molecule 2; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Glutamate; Glutamate decarboxylase; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - immunology; Humans; Insulin resistance; Latent Autoimmune Diabetes in Adults - genetics; Latent Autoimmune Diabetes in Adults - immunology; latent autoimmune diabetes of adults; Lymphocytes; Male; Mexico; Mexico - epidemiology; Middle Aged; Obesity; Obesity in children; Phenotype; Polymorphism, Single Nucleotide; Type 1 diabetes; Type 2 diabetes; Mexico; China; Connecticut; fas apoptotic inhibitory molecule 2; Mexico; latent autoimmune diabetes of adults; genome-wide association study
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251810154

Latent autoimmune diabetes in adults (LADA) is characterized by the presence of glutamate decarboxylase autoantibodies (GADA). LADA has intermediate features between type 1 diabetes and type 2 diabetes. In addition, genetic risk factors for both types of diabetes are present in LADA. Nonetheless, evidence about the genetics of LADA in non-European populations is scarce. This study aims to perform a genome-wide association study with a phenome-wide association study of LADA in a southeastern Mexican population. We included 59 patients diagnosed with LADA from a previous study and 3121 individuals without diabetes from the MxGDAR/ENCODAT database. We utilized the GENESIS package in R to perform the genome-wide association study (GWAS) of LADA and PLINK for the phenome-wide association study (PheWAS) of LADA features. Nine polymorphisms reach the nominal association level (1 × 10 ) in the GWAS. The PheWAS showed that rs7305229 is genome-wide and associated with serum GADA levels in our sample ( = 1.84 × 10 ). rs7305229 is located downstream of the FAIM2 gene; previous reports associate FAIM2 variants with childhood obesity, body mass index, body adiposity measures, lymphocyte CD8+ activity, and anti-thyroid peroxidase antibodies. Our findings reveal that rs7305229 affects the GADA levels in patients with LADA from southeastern Mexico. More studies are needed to determine if this risk genotype exists in other populations with LADA.