Abstract 008: Genomic and Epigenomic Integration Reveals LY86 as an Important Gene for Obesity
Background Emerging evidence shows that both genetics and epigenetics play important roles in the pathogenesis of obesity. We predicted that integration of genomic and epigenomic data would increase power in prioritizing top signals related to obesity.
Methods We did a literature search to identify genes discovered by genome-wide association studies (GWAS) for obesity-related traits (i.e. obesity, body mass index, waist-hip ratio, waist, weight and hip) and genes related to extreme forms of obesity. Then, we analyzed if the methylation levels of these genes were also associated with obesity in an epigenome-wide association study (EWAS), which used Illumina HumanMethylation27 BeadChip. We examined an initial cohort of 7 adolescent obese cases and 7 age-matched lean controls, followed by two replication cohorts of youth (46 vs. 46 and 230 cases vs. 413 controls, respectively, Table 1).
Results The promoter region of the lymphocyte antigen 86 (LY86) gene showed hypermethylation in the obese in the initial cohort (p=0.009), which was validated in both replication cohorts (p<0.05). There was no significant difference of this association between African- and European-Americans, males and females. In silico analysis revealed that this region was specifically enriched with binding sites for obesity-related transcription factors. Moreover, the methylation levels of this region were also significantly correlated with several metabolic traits as well as body mass index and total percentage of body fat independent of obesity.
Conclusions By integrating recent GWAS and EWAS findings, we identified the LY86 gene as an important regulator in the pathophysiology of obesity. Our study emphasizes the importance of integrating genomic and epigenomic information to improve identification and functional insight of genes relevant for complex diseases.
- © 2013 by American Heart Association, Inc.