Genome-wide association study on overweight in Brazilian children with asthma: Old stories and new discoveries.

Abstract

Introduction: Overweight and obesity are chronic and multifactorial diseases with a strong genetic component contributing to weight gain across all age groups. This study aimed to conduct a Genome-wide Association Study (GWAS) on a cohort of 1,004 Brazilian children (5-11 years old) to identify specific DNA regions associated with susceptibility to overweight.

Methods: The GWAS was performed on children participating in the SCAALA (Asthma and Allergy Social Changes in Latin America) program, with participants classified as either overweight or non-overweight. Genotyping was carried out using the Illumina 2.5 Human Omni bead chip. Using ELISA, cytokine levels (IL-5, IL-13, IL-10, and IFN) were measured in the blood culture supernatant. Furthermore, pathway analyses were conducted utilizing the Gene Ontology tool.

Results: Our analysis revealed eight significant signals distributed across the genome. The most prominent single nucleotide variant (SNV) was identified in the IL1R1 gene, followed by three variants in the LOC105377841 region (located between the ADH5P4 and EYS genes), as well as variants in the KNTC1, RAPTOR, and DSCAM genes. Among the identified variants, three (IL1R1, RAPTOR, and DSCAM) are associated with immune mechanisms, one (ST18) is linked to the death pathway, and one (KNTC1) is associated with mitotic spindle assembly. The genetic risk score analysis demonstrated that having one or more variants among the six analyzed significantly increased the risk of being overweight by eightfold.

Conclusions: Our study uncovered genetic loci within pathways with strong biological plausibility, including identifying a novel region (LOC105377841) not previously associated with overweight. Understanding the genetic variants involved in overweight and obesity is crucial for advancing our knowledge of these diseases, particularly within mixed populations such as the Brazilian population.