Year: 2019
Type: article
Study design: Observational Study
Abstract: Objective We investigated gene interactions (epistasis) for body mass index (BMI) in a European-American adult female cohort via genome-wide interaction analyses (GWIA) and pathway association analyses. Methods Genome-wide pairwise interaction analyses were carried out for BMI in 493 extremely obese cases (BMI>35 kg/m2) and 537 never-overweight controls (BMI<25 kg/m2). To further validate the results, specific SNPs were selected based on the GWIA results for haplotype-based association studies. Pathway-based association analyses were performed using a modified Gene Set Enrichment Algorithm (GSEA) (GenGen program) to further explore BMI-related pathways using our genome wide association study (GWAS) data set, GIANT, ENGAGE, and DIAGRAM Consortia. Results The EXOC4-1q23.1 interaction was associated with BMI, with the most significant epistasis between rs7800006 and rs10797020 (P = 2.63x10-11). In the pathway-based association analysis, Tob1 pathway showed the most significant association with BMI (empirical P<0.001, FDR= 0.044, FWER=0.040). These findings were further validated in different populations. Conclusions Genome-wide pairwise SNP-SNP interaction and pathway analyses suggest that EXOC4 and TOB1-related pathways may contribute to the development of obesity.
Source: Frontiers in Genetics
Authors: Hongxiao Jiao, Yong Zang, Miaomiao Zhang, Yuan Zhang, Yaogang Wang, Kai Wang, R. Arlen Price, Wei-Dong Li
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Foundation for the National Institutes of Health, American Heart Association, Children's Hospital of Philadelphia, National Natural Science Foundation of China, Tianjin Science and Technology Committee, Tianjin Medical University, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W2942924627