Phenome-Wide Association Study of Latent Autoimmune Diabetes from a Southern Mexican Population Implicates rs7305229 with Plasmatic Anti-Glutamic Acid Decarboxylase Autoantibody (GADA) Levels
Por:
Nolasco-Rosales G.A., Martínez-Magaña J.J., Juárez-Rojop I.E., Rodríguez-Sánchez E., Ruiz-Ramos D., Villatoro-Velázquez J.A., Bustos-Gamiño M., Medina-Mora M.E., Tovilla-Zárate C.A., Cruz-Castillo J.D., Nicolini H., Genis-Mendoza A.D.
Publicada:
1 ene 2024
Resumen:
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 × 10-5) in the GWAS. The PheWAS showed that rs7305229 is genome-wide and associated with serum GADA levels in our sample (p = 1.84 × 10-8). 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. © 2024 by the authors.
Filiaciones:
Nolasco-Rosales G.A.:
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, 86100, Mexico
Martínez-Magaña J.J.:
Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, 06520, CT, United States
VA Connecticut Healthcare System, West Haven, 06516, CT, United States
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, 06516, CT, United States
Juárez-Rojop I.E.:
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, 86100, Mexico
Rodríguez-Sánchez E.:
Hospital Regional de Alta Especialidad “Dr. Gustavo A. Rovirosa Pérez”, Secretaría de Salud, Villahermosa, 86020, Mexico
Ruiz-Ramos D.:
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, 86100, Mexico
Villatoro-Velázquez J.A.:
Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz, Secretaría de Salud, Mexico, 14370, Mexico
Bustos-Gamiño M.:
Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz, Secretaría de Salud, Mexico, 14370, Mexico
Medina-Mora M.E.:
Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz, Secretaría de Salud, Mexico, 14370, Mexico
Facultad de Psicología, Universidad Nacional Autónoma de México—UNAM, Mexico, 04510, Mexico
Tovilla-Zárate C.A.:
División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Villahermosa, 86658, Mexico
Cruz-Castillo J.D.:
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, 86100, Mexico
Nicolini H.:
Laboratorio de Enfermedades Psiquiátricas, Neurodegenerativas y Adicciones, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico, 14610, Mexico
Genis-Mendoza A.D.:
Laboratorio de Enfermedades Psiquiátricas, Neurodegenerativas y Adicciones, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico, 14610, Mexico
gold, All Open Access; Gold Open Access
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