Regular exercise, alcohol consumption, and smoking interact with the polygenetic risk scores involved in insulin sensitivity and secretion for the risk of concurrent hyperglycemia, hypertension, and dyslipidemia.

Objectives: 3GO, defined as the simultaneous presence of hypertension, hyperglycemia, and dyslipidemia, is rising in Asians. We determined polygenetic risk scores (PRS) for 3GO risk and the interactions between PRS and lifestyle habits on 3GO risk in Korean adults aged 40 to 77 y recruited from the urban hospital cohort of the Korean Genomic and Epidemiology Study (KoGES), conducted from 2004 to 2013.

Methods: Participants were divided into a group with 3GO (n = 570) and a group without any of the three components of 3GO (0GO; n = 14 155). A genome-wide association study revealed genetic variants, and generalized multifactor dimensionality reduction was used to identify the best model of interaction between genetic variant and gene variant. The PRS was calculated from the genetic variants in the best model, and the effects of PRS interactions with lifestyles on 3GO risk were investigated.

Results: The PRS for 3GO risk was calculated from five genetic variants: CTNNA2_rs17018376, PPP2R2C_rs6835336, CDKAL1_rs12662218, ADCY8_rs1329797, and KCNQ1_rs2237892. After adjustment for lifestyle, a high PRS was found to increase the risk of 3GO by 2.567-fold (95% confidence interval [CI], 1.917-3.437) as compared with controls (P < 0.001). PRS interacted with serum glucose (odds ratio, 2.283; 95% CI, 1.557-3.347), low high-density lipoprotein (odds ratio, 2.605; 95% CI, 1.701-3.991), and triacylglycerol concentration (odds ratio, 2.468; 95% CI, 1.630-3.737; P < 0.001). Interactions between PRS and alcohol (P < 0.0001), exercise (P = 0.035), and smoking (P = 0.006) significantly affected 3GO risk. PRSs were significantly correlated with 3GO risk among smokers, alcohol drinkers, and those who exercised infrequently.

Conclusions: PRSs calculated using a PRS model based on five single-nucleotide polymorphisms revealed that insulin sensitivity and secretion were significantly associated with 3GO risk. Furthermore, reducing alcohol intake, exercising regularly, and quitting smoking might be effective for reducing 3GO risk in individuals with a high PRS.