Polygenetic Variants Related to Osteoarthritis Risk and Their Interactions with Energy, Protein, Fat, and Alcohol Intake in Adults in a Large Cohort

Abstract

Osteoarthritis (OA) is increasing globally, especially among elderly Asian women, and its increase may be due to the interaction between genetic factors and lifestyle. This study tested the hypothesis that polygenetic variants associated with OA risk interacted with lifestyle in adults over 40 years in the Ansan–Ansung cohort. Genetic variants were chosen through a genome-wide association study with OA participants (case; n = 580) and controls without arthritis (n = 4850). Genetic variants with interactions were selected by a generalized multifactor dimensionality reduction. The best model’s polygenic risk scores (PRS) were calculated by summing the number of risk alleles in the selected genetic variants. The best five single nucleotide polymorphism (SNP) model included AIG1_rs6570550, COX10_rs62054459, DLG2_rs148643344, SOX5_rs73283615, and PLXNA4_rs1472529430, while IL12A_ rs1491318751 was added to the five-SNP model to produce a six-SNP model. Only COX10_rs62054459 in subcutaneous and visceral adipose tissue was associated with COX10 protein expression. The participants, having high-PRS from the five-SNP and six-SNP models, were at a higher OA risk than those with low-PRS by 3.88 and 4.42 times, respectively. The PRS was not associated with metabolic syndrome or with the insulin resistance index (HOMA-IR). Energy, protein, fat, alcohol, and a Western-style diet intake interacted with the PRS to influence OA risk (p = 0.005, 0.042, and 0.021, respectively). In the high energy and alcohol intake and low protein, fat, Western-style diet intake, the participants with a high-PRS had a higher incidence of OA than those with low-PRS. In conclusion, the adults with a high-PRS were at a higher OA risk. Particularly, adults with high PRS should have a lower energy intake, higher WSD containing higher protein and fat intake, and moderate alcohol intake to alleviate OA risk. These results can be applied to personalized nutrition plans to decrease OA risk.