Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study
Hypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/15/17/3850 |
| _version_ | 1797582043784151040 |
|---|---|
| author | Da Sol Kim Sunmin Park |
| author_facet | Da Sol Kim Sunmin Park |
| author_sort | Da Sol Kim |
| collection | DOAJ |
| description | Hypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk in 56,664 participants aged >40 in a hospital-based cohort. The participants were classified as having hypothyroidism (n = 870) diagnosed by a physician and no hypothyroidism (n = 55,794). Genetic variants associated with hypothyroidism were identified using a genome-wide association study (GWAS). Genetic variants interacting with each other were selected using a generalized multifactor dimensionality reduction analysis, and the PRS generated was evaluated for interaction with lifestyle parameters. Coffee, alcohol, meat intake, and a Korean balanced diet were inversely associated with hypothyroidism risk, as were selenium, copper, and manganese intakes. White blood cell (WBC) counts and serum alkaline phosphatase and triglyceride concentrations were positively associated with hypothyroidism risk, as were osteoporosis and thyroid cancer. The GMDR analysis generated a three-single nucleotide polymorphism (SNP) model comprising dual oxidase-1 (<i>DUOX1</i>)_rs1648314; thyroid-stimulating hormone receptor (<i>TSHR</i>)_rs75664963; and major histocompatibility complex, class-II, DQ Alpha-1 (<i>HLA-DQA1</i>)_rs17426593. The PRS derived from the three- and seven-SNP models were associated with a 2.11- and 2.32-fold increase in hypothyroidism risk, respectively. Furthermore, the PRS from the three-SNP model showed interactions with WBC counts, wherein the positive association with hypothyroidism risk was more pronounced in participants with low WBC counts than those with high WBC counts (≥4 × 10<sup>9</sup> /L). Dietary patterns, such as the plant-based diet (PBD) and the Western-style diet (WSD), along with smoking status, exhibited interactions with the PRS, influencing hypothyroidism risk. In participants with a high PRS, those in the high-PBD, low-WSD, and smoker groups had a higher proportion of hypothyroidism than those in the low-PBD, high-WSD, and non-smoker groups. In conclusion, genetic variants related to immunity and thyroid hormone secretion were linked to hypothyroidism risk, and their PRS interacted with PBD and WSD intake and smoking status. These results contribute to a better understanding of hypothyroidism and its prevention strategies for precision medicine intervention. |
| first_indexed | 2024-03-10T23:15:15Z |
| format | Article |
| id | doaj.art-449d7fc0489e47a98221df2448b60795 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T23:15:15Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-449d7fc0489e47a98221df2448b607952023-11-19T08:40:01ZengMDPI AGNutrients2072-66432023-09-011517385010.3390/nu15173850Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort StudyDa Sol Kim0Sunmin Park1Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of KoreaDepartment of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of KoreaHypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk in 56,664 participants aged >40 in a hospital-based cohort. The participants were classified as having hypothyroidism (n = 870) diagnosed by a physician and no hypothyroidism (n = 55,794). Genetic variants associated with hypothyroidism were identified using a genome-wide association study (GWAS). Genetic variants interacting with each other were selected using a generalized multifactor dimensionality reduction analysis, and the PRS generated was evaluated for interaction with lifestyle parameters. Coffee, alcohol, meat intake, and a Korean balanced diet were inversely associated with hypothyroidism risk, as were selenium, copper, and manganese intakes. White blood cell (WBC) counts and serum alkaline phosphatase and triglyceride concentrations were positively associated with hypothyroidism risk, as were osteoporosis and thyroid cancer. The GMDR analysis generated a three-single nucleotide polymorphism (SNP) model comprising dual oxidase-1 (<i>DUOX1</i>)_rs1648314; thyroid-stimulating hormone receptor (<i>TSHR</i>)_rs75664963; and major histocompatibility complex, class-II, DQ Alpha-1 (<i>HLA-DQA1</i>)_rs17426593. The PRS derived from the three- and seven-SNP models were associated with a 2.11- and 2.32-fold increase in hypothyroidism risk, respectively. Furthermore, the PRS from the three-SNP model showed interactions with WBC counts, wherein the positive association with hypothyroidism risk was more pronounced in participants with low WBC counts than those with high WBC counts (≥4 × 10<sup>9</sup> /L). Dietary patterns, such as the plant-based diet (PBD) and the Western-style diet (WSD), along with smoking status, exhibited interactions with the PRS, influencing hypothyroidism risk. In participants with a high PRS, those in the high-PBD, low-WSD, and smoker groups had a higher proportion of hypothyroidism than those in the low-PBD, high-WSD, and non-smoker groups. In conclusion, genetic variants related to immunity and thyroid hormone secretion were linked to hypothyroidism risk, and their PRS interacted with PBD and WSD intake and smoking status. These results contribute to a better understanding of hypothyroidism and its prevention strategies for precision medicine intervention.https://www.mdpi.com/2072-6643/15/17/3850hypothyroidismwhite blood cell countsimmunityinflammationdiet pattern |
| spellingShingle | Da Sol Kim Sunmin Park Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study Nutrients hypothyroidism white blood cell counts immunity inflammation diet pattern |
| title | Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study |
| title_full | Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study |
| title_fullStr | Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study |
| title_full_unstemmed | Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study |
| title_short | Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study |
| title_sort | interactions between polygenetic variants and lifestyle factors in hypothyroidism a hospital based cohort study |
| topic | hypothyroidism white blood cell counts immunity inflammation diet pattern |
| url | https://www.mdpi.com/2072-6643/15/17/3850 |
| work_keys_str_mv | AT dasolkim interactionsbetweenpolygeneticvariantsandlifestylefactorsinhypothyroidismahospitalbasedcohortstudy AT sunminpark interactionsbetweenpolygeneticvariantsandlifestylefactorsinhypothyroidismahospitalbasedcohortstudy |