UNRAVELLING PUTATIVE ETHNIC-SPECIFIC OBESITY LOCI IN MALAYSIAN YOUTHS: A PRELIMINARY GENOME-WIDE ASSOCIATION STUDY

Abstract

Obesity is a major global health problem that increases the risk of various chronic diseases, such as cancer and type 2 diabetes. Understanding the genetic factors that contribute to obesity is essential for developing effective interventions. Thus, we aim to identify obesity-associated variants in Malaysian youth populations. In this study, we conducted a preliminary genome-wide association analysis on a genotyped dataset imputed with established Asian-specific obesity-associated single variants and the 1000 Genomes data of 240 Malaysian youths (aged 18-30 years), to identify susceptibility loci associated with obesity (BMI-based measurement). Statistical analysis including linear regression and case control association were conducted to determine the association between single nucleotide polymorphisms and obesity. While no common variants achieved genome-wide significance (P < 5 x 10^-8), 24 variants however, exhibited suggestive significance (P < 1.52 x 10^-6). Notably, three chromosomal regions stood out (7p11.2, 3q29, and 2p25.3), harbouring multiple suggestively associated genetic variants. We highlighted the potential roles of these variants in influencing obesity-related pathways, notably the EGFR-gut microbiota axis, the HES1-Notch signalling link, and the neurofibrillary tangles-testosterone connection. We posit plausible mechanisms based on these genes, illuminating pathways influencing weight gain. These findings shed light to the ethnic-specific obesity loci in Malaysia, suggesting a promising direction for personalised medicine approaches in Malaysian youth population. This study advances our knowledge of the genetic basis of obesity and paves way for valuable insights of targeted interventions and precision medicine strategies to combat the obesity epidemic.