Impact of Lung-Related Polygenic Risk Scores on Chronic Obstructive Pulmonary Disease Risk and Their Interaction with w-3 Fatty Acid Intake in Middle-Aged and Elderly Individuals

• Published in: Nutrients 2023-07, Vol.15 (13), p.3062
• Main Authors: Kim, Ki-Song, Park, Sunmin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Air flow; Alcohol use; Body fat; C-reactive protein; Caffeine; Calcium channels (voltage-gated); Chronic obstructive pulmonary disease; Coffee; Development and progression; Education; Ethnicity; Ethylenediaminetetraacetic acid; Exercise; Fatty Acids; Food; Forced Expiratory Volume; Genetic aspects; Genetic diversity; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Growth factors; GTPase-Activating Proteins - genetics; Health aspects; Health risks; Humans; inflammation; Interaction models; Lifestyles; Lung; Lung diseases; Lung diseases, Obstructive; lung function; lung structure; Middle age; Middle Aged; Obstructive lung disease; Older people; Physical fitness; polygenic risk score; Precision medicine; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - genetics; Questionnaires; Review boards; Risk; Risk Factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Smoking; Spirometry; Vital Capacity
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15133062

Chronic obstructive pulmonary disease (COPD) is a complex, progressive respiratory disorder with persistent airflow limitation and tissue destruction. We aimed to explore the genetic impact of COPD and its interaction with nutrient intake in 8840 middle-aged and elderly individuals from the Ansan/Ansung cohorts. Participants were diagnosed with COPD if the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) was less than 0.7 using spirometry, and if they were previously diagnosed with COPD by a physician. Genome-wide association studies (GWAS) were performed to screen for genetic variants associated with COPD risk. Among them, we selected the genetic variants that exhibited interactions using the generalized multifactor dimensionality reduction (GMDR) method. The polygenic risk score (PRS) was computed by summing the number of risk alleles in the SNP-SNP interaction models that adhered to specific rules. Subsequently, participants were categorized into low-PRS, medium-PRS, and high-PRS groups. The participants with COPD exhibited significantly lower FEV1/FVC ratios (0.64) than those without COPD (0.82). It was positively associated with inflammation markers (serum C-reactive protein and white blood cell levels). A higher proportion of COPD participants were smokers and engaged in regular exercise. The 5-SNP model consisted of _rs1585258, _rs1997571, _rs719601, _rs10405598, and _rs889294, and showed a significant association with COPD risk ( < 0.001). Participants in the high-PRS group of this model had a 2.2-fold higher risk of COPD than those in the low-PRS group after adjusting for covariates. The PRS interacted with w-3 fatty acid intake and exercise, thus influencing the risk of COPD. There was an increase in COPD incidence among individuals with a higher PRS, particularly those with low consumption of w-3 fatty acid and engaged in high levels of exercise. In conclusion, adults with a high-PRS are susceptible to COPD risk, and w-3 fatty acid intake and exercise may impact the risk of developing COPD, potentially applying to formulate precision medicines to prevent COPD.