UBE2L3 and Insulin resistance: We combined this hub gene analysis with GWAS association gene scores, and observed that PSMB5, UBE2L3, and PSMD3 (Fig 5C, S9 Table) are important in many age-related diseases or phenotypes, such as Alzheimer’s disease, HDL cholesterol, LDL cholesterol, triglycerides, and insulin resistance.