Glycogenome Signatures in Complex Cardiometabolic Disease (789.4)

Cardiometabolic diseases (CMDs) are a leading cause of death. Because of the fundamental roles of glycogenes in cell interactions and tissue remodeling, we hypothesized that a focused interrogation of the human glycogenome in genome wide association studies (GWAS) for CMDs would reveal a role for previously unrecognized glycogenes. We defined a set of 723 human glycogenes, and annotated ~45,000 single nucleotide polymorphisms (hg 19, dbSNP build 137) into these genes, from 16 GWAS datasets for CMD traits, including coronary artery disease, plasma lipids and type 2 diabetes. At a false discovery rate of 5%, we identified 788 SNPs in 83 genes associated with one or more of 11 traits. Of these, 334 SNPs in 36 glycogenes were also significant at a Bonferroni‐adjusted p < 0.05 (unadjusted p < ~10‐6). A weighted score of SNP associations across traits revealed several glycogenes with pleiotropic associations, including COL4A3BP, ABO, PIGU, ST3GAL4, GCK, SDCBP, G6PC2, and FUT2. Our analyses suggest a role for multiple glycogenes in diverse CMDs with specific glycogenes contributing to multiple traits. Functional studies and therapeutic targeting of specific glycogenes and pathways in CMD are warranted.Grant Funding Source: Supported by the National Institutes of Health (U01‐HL108636 and K24‐HL10763)