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Updated: Jun 11, 2026

Large-Scale Multi-Omics Genome-Wide Association Studies (Mo-GWAS): Guidelines for Sample Preparation and Normalization
Published on: July 27, 2021
Genome-wide association and MaODR-based multi-locus interaction analyses reveal a susceptibility gene network for
Yu-Da Lin1,2, Kuei-Hau Luo3, Li-Yeh Chuang4
1Department of Business Computing, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan.
Background:
Metabolic syndrome involves several lipid-related genes, including apolipoprotein A5 (APOA5), lipoprotein lipase (LPL), and cholesteryl ester transfer protein (CETP). Although individual SNP susceptibility has been reported, gene-gene interactions remain underexplored. To address this gap, we apply many-objective multifactor dimensionality reduction (MaODR)-previously developed by our group-to detect gene‒gene interactions in unbalanced newly identified MetS and non-MetS subjects.
Results:
Among 40,773 Taiwan Biobank participants (5,723 newly identified metabolic syndrome cases and 35,050 controls) after excluding smokers and individuals with chronic diseases, genome-wide association analysis identifies 35 significant SNPs. We detect a two-locus SNP-SNP interaction between APOA5 and LPL; the most significant genotype combination is rs331-GG with rs651821-CC (bootstrap odds ratio = 1.76; p = 9.61 × 10⁻2⁰). MaODR also reveals a three-way interaction among APOA5, LPL, and CETP. Furthermore, we find that the LPL, APOA5, BUD13, zinc finger protein 1 (ZPR1), APOC3, CETP, and APOE genes collectively contributed to MetS susceptibility, with SNPs of LPL showing a significant metabolic syndrome-associated effect and interacting with SNPs of the APOA5 and CETP genes. Genes linked to metabolic syndrome are enriched in cholesterol metabolism and the peroxisome proliferator-activated receptor signaling pathway.
Conclusions:
MaODR detects epistasis networks through SNP-SNP interactions in newly identified metabolic syndrome, highlighting APOA5-LPL and APOA5-LPL-CETP interaction models.
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