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

Germán Alberto Nolasco-Rosales; José Jaime Martínez-Magaña; Isela Esther Juárez-Rojop; Ester Rodríguez-Sánchez; David Ruiz-Ramos; Jorge Ameth Villatoro-Velázquez; Marycarmen Bustos-Gamiño; Maria Elena Medina-Mora; Carlos Alfonso Tovilla-Zárate; Juan Daniel Cruz-Castillo; Humberto Nicolini; Alma Delia Genis-Mendoza

doi:10.20944/preprints202409.0287.v1

Preprint Article Version 1 This version is not peer-reviewed

Version 1 : Received: 2 September 2024 / Approved: 3 September 2024 / Online: 4 September 2024 (12:56:08 CEST)

Latent autoimmune diabetes in adults (LADA) is characterized by the presence of glutamate de-carboxylase 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 GWAS of LADA and PLINK for the PheWAS of LADA features. Nine polymorphisms reach the nominal association level (1x10-5) in the GWAS. The PheWAS showed that rs7305229 is genome-wide associated with serum GADA levels in our sample (p=1.84x10-8). rs7305229 is located downstream 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.

Latent Autoimmune Diabetes of Adults; Genome-Wide Association Study; Mexico; Fas apoptotic inhibitory molecule 2

Medicine and Pharmacology, Endocrinology and Metabolism

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

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