For a study, the researchers aimed to provide the first statistically adequately powered relationship between common risk alleles and the occurrence of degenerative disc disease (DDD) in the Eastern US population. Utilization of the Mass General Brigham (MGB) Biobank in which subjects’ Medical Record was linked with genotyped data from single-nucleotide polymorphism (SNP) arrays was done. Subjects with lumbosacral spine magnetic resonance (MR) imaging reports were used to construct the Cases cohort; the Biobank’s Controls cohort was used as the control cohort. About 414 subjects (mean age=64, range=27 to 94) were Cases and 925 Controls (mean age=46, range=21–61). A systematic search identified 25 SNPs in 18 genes in the SNP arrays. At univariate level, rs1544410 in VDR was significantly related with DDD for male subjects (odds ratio [OR] = 0.594, P=0.011). After adjustment for all effective variants and demographics, three predictor variables had an affective relation with the outcome, age (OR=1.130, q<0.0001), rs1,43,383 (OR=1.951, q=0.056), and rs37,37,821 (OR=2.701, q=0.069). A novel variant-to-variant correlation rs1,43,383:rs7,63,110 was significantly adjusted OR=7.933, q=0.070). According to the studies of common variants’ correlation with the presence of DDD in the Northeast United States, it was found that a novel and effective variant-to-variant interaction is related to the risk of developing DDD, corroborating and necessitating the inclusion of gene-gene interactions in predictive risk model development for DDD.