{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:47:07Z","timestamp":1781606827940,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T00:00:00Z","timestamp":1693699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["RS-2023-00208567"],"award-info":[{"award-number":["RS-2023-00208567"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 &gt;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 (DUOX1)_rs1648314; thyroid-stimulating hormone receptor (TSHR)_rs75664963; and major histocompatibility complex, class-II, DQ Alpha-1 (HLA-DQA1)_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 (\u22654 \u00d7 109 \/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.<\/jats:p>","DOI":"10.3390\/nu15173850","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:43:20Z","timestamp":1693795400000},"page":"3850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Da Sol","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8340","authenticated-orcid":false,"given":"Sunmin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s12325-019-01080-8","article-title":"Hypothyroidism in Context: Where We\u2019ve Been and Where We\u2019re Going","volume":"36","author":"Chiovato","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13044-019-0063-3","article-title":"Hypothyroidism in the older population","volume":"12","author":"Leng","year":"2019","journal-title":"Thyroid. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/S0140-6736(17)30703-1","article-title":"Hypothyroidism","volume":"390","author":"Chaker","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sawicka-Gutaj, N., Erampamoorthy, A., Zybek-Kocik, A., Kyriacou, A., Zgorzalewicz-Stachowiak, M., Czarnywojtek, A., and Rucha\u0142a, M. (2022). The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis. Metabolites, 12.","DOI":"10.3390\/metabo12040336"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cca.2022.01.006","article-title":"Hyperlipidemia and hypothyroidism","volume":"527","author":"Su","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s42000-020-00267-x","article-title":"Genetics of primary congenital hypothyroidism\u2014A review","volume":"20","author":"Kostopoulou","year":"2021","journal-title":"Hormones"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1210\/jc.2017-00832","article-title":"DUOX2 Mutations Are Associated with Congenital Hypothyroidism With Ectopic Thyroid Gland","volume":"102","author":"Kizys","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/ped4.12324","article-title":"Genetics of congenital hypothyroidism: Modern concepts","volume":"6","author":"Stoupa","year":"2022","journal-title":"Pediatr. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Babi\u0107 Leko, M., Gunja\u010da, I., Plei\u0107, N., and Zemunik, T. (2021). Environmental Factors Affecting Thyroid-Stimulating Hormone and Thyroid Hormone Levels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126521"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.mpdhp.2020.02.003","article-title":"Environmental factors and anatomic pathology of the thyroid gland: Review of literature","volume":"26","author":"Gonzalez","year":"2020","journal-title":"Diagn. Histopathol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bellastella, G., Scappaticcio, L., Caiazzo, F., Tomasuolo, M., Carotenuto, R., Caputo, M., Arena, S., Caruso, P., Maiorino, M.I., and Esposito, K. (2022). Mediterranean Diet and Thyroid: An Interesting Alliance. Nutrients, 14.","DOI":"10.3390\/nu14194130"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.nut.2016.07.001","article-title":"Interaction of BDNF rs6265 variants and energy and protein intake in the risk for glucose intolerance and type 2 diabetes in middle-aged adults","volume":"33","author":"Daily","year":"2017","journal-title":"Nutrition"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12986-016-0096-8","article-title":"Interactions with the MC4R rs17782313 variant, mental stress and energy intake and the risk of obesity in Genome Epidemiology Study","volume":"13","author":"Park","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.3346\/jkms.2015.30.9.1279","article-title":"Self-rated Subjective Health Status Is Strongly Associated with Sociodemographic Factors, Lifestyle, Nutrient Intakes, and Biochemical Indices, but Not Smoking Status: KNHANES 2007\u20132012","volume":"30","author":"Park","year":"2015","journal-title":"J. Korean Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00394-018-1719-9","article-title":"Carrying minor allele of FADS1 and haplotype of FADS1 and FADS2 increased the risk of metabolic syndrome and moderate but not low fat diets lowered the risk in two Korean cohorts","volume":"58","author":"Park","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.clnu.2015.09.010","article-title":"Very-low-fat diets may be associated with increased risk of metabolic syndrome in the adult population","volume":"35","author":"Park","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_17","first-page":"47","article-title":"TRPV1 Gene Polymorphisms Are Associated with Type 2 Diabetes by Their Interaction with Fat Consumption in the Korean Genome Epidemiology Study","volume":"9","author":"Park","year":"2016","journal-title":"J. Nutr. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hur, H.J., Yang, H.J., Kim, M.J., Lee, K.H., Kim, M.S., and Park, S. (2022). Association of Polygenic Variants with Type 2 Diabetes Risk and Their Interaction with Lifestyles in Asians. Nutrients, 14.","DOI":"10.3390\/nu14153222"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1038\/sj.ejcn.1602657","article-title":"Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study","volume":"61","author":"Ahn","year":"2007","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_20","unstructured":"Steel, R.G., Torrie, J.H., and Dickey, D.A. (1997). Principles and Procedures of Statistics: A Biological Approach, McGraw-Hill."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kim, J.O., and Mueller, C.W. (1978). Factor Analysis. Statistical Methods and Practical Issues, Sage publications.","DOI":"10.4135\/9781412984256"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"861880","DOI":"10.3389\/fnut.2022.861880","article-title":"Beneficial Effects of a Low-Glycemic Diet on Serum Metabolites and Gut Microbiota in Obese Women with Prevotella and Bacteriodes Enterotypes: A Randomized Clinical Trial","volume":"9","author":"Hur","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/jmwh.13358","article-title":"Hypothyroidism: Diagnosis and Evidence-Based Treatment","volume":"67","author":"Davis","year":"2022","journal-title":"J. Midwifery Womens Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1530\/rep.0.1260371","article-title":"Effect of hypothyroidism on hormone profiles in virgin, pregnant and lactating rats, and on lactation","volume":"126","author":"Hapon","year":"2003","journal-title":"Reproduction"},{"key":"ref_25","first-page":"123","article-title":"Hypothyroidism and women's health","volume":"47","author":"Redmond","year":"2002","journal-title":"Int. J. Fertil. Womens Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1097\/GME.0000000000001811","article-title":"Effects of oral versus transdermal estradiol plus micronized progesterone on thyroid hormones, hepatic proteins, lipids, and quality of life in menopausal women with hypothyroidism: A clinical trial","volume":"28","author":"Kaminski","year":"2021","journal-title":"Menopause"},{"key":"ref_27","first-page":"311","article-title":"Thyroid Dysfunction in Periand Postmenopausal Women-Cumulative Risks","volume":"120","author":"Raue","year":"2023","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kim, S., Kwon, Y.S., Kim, J.Y., Hong, K.H., and Park, Y.K. (2019). Association between Iodine Nutrition Status and Thyroid Disease-Related Hormone in Korean Adults: Korean National Health and Nutrition Examination Survey VI (2013\u20132015). Nutrients, 11.","DOI":"10.3390\/nu11112757"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5720\/kjcn.2021.26.1.48","article-title":"Estimation of Dietary Iodine Intake of Koreans through a Total Diet Study (TDS)","volume":"26","author":"Lee","year":"2021","journal-title":"Korean J. Community Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Katagiri, R., Yuan, X., Kobayashi, S., and Sasaki, S. (2017). Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173722"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wu, K., Zhou, Y., Ke, S., Huang, J., Gao, X., Li, B., Lin, X., Liu, X., Liu, X., and Ma, L. (2021). Lifestyle is associated with thyroid function in subclinical hypothyroidism: A cross-sectional study. BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00772-z"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1007\/s00394-018-1837-4","article-title":"Non-immune-related hypothyroidism and its relationship with excess iodine","volume":"58","author":"Kim","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1530\/EJE-12-0356","article-title":"Moderate alcohol consumption may protect against overt autoimmune hypothyroidism: A population-based case-control study","volume":"167","author":"Pedersen","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3803\/EnM.2016.31.2.213","article-title":"Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease","volume":"31","author":"Wiersinga","year":"2016","journal-title":"Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1188547","DOI":"10.3389\/fendo.2023.1188547","article-title":"Effect of coffee consumption on thyroid function: NHANES 2007\u20132012 and Mendelian randomization","volume":"14","author":"Zhao","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yan, Y., Xu, M., Wu, M., Wang, X., Li, F., Zhang, J., You, L., Pan, X., Feng, W., and Wu, J. (2022). Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: A cross-sectional study. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00981-0"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.3389\/fimmu.2019.02349","article-title":"The Impact of Obesity on Thyroid Autoimmunity and Dysfunction: A Systematic Review and Meta-Analysis","volume":"10","author":"Song","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1007\/s13300-019-00700-4","article-title":"Thyroid Dysfunction and Type 2 Diabetes Mellitus: Screening Strategies and Implications for Management","volume":"10","author":"Kalra","year":"2019","journal-title":"Diabetes Ther."},{"key":"ref_39","first-page":"e210002","article-title":"Update on dyslipidemia in hypothyroidism: The mechanism of dyslipidemia in hypothyroidism","volume":"11","author":"Liu","year":"2022","journal-title":"J. Endocr. Connect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12944-022-01749-0","article-title":"Assessment of the relationship between subclinical hypothyroidism and blood lipid profile: Reliable or not?","volume":"21","author":"Luo","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Izquierdo, J., Filion, K.B., Boivin, J.F., Azoulay, L., Pollak, M., and Yu, O.H.Y. (2020). Subclinical hypothyroidism and the risk of cancer incidence and cancer mortality: A systematic review. BMC Endocr. Disord., 20.","DOI":"10.1186\/s12902-020-00566-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.breast.2023.02.008","article-title":"Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis","volume":"68","author":"Solmunde","year":"2023","journal-title":"Breast"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"R217","DOI":"10.1530\/ERC-21-0159","article-title":"Congenital hypothyroidism and thyroid cancer","volume":"28","author":"Penna","year":"2021","journal-title":"J. Endocr. Relat. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"288","DOI":"10.2174\/1871530315666150619094242","article-title":"Selenium and Iodine in Autoimmune Thyroiditis","volume":"15","author":"Guastamacchia","year":"2015","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1530\/EJE-15-0617","article-title":"The relationship between oxidative stress and autoimmunity in Hashimoto's thyroiditis","volume":"173","author":"Ates","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_46","first-page":"326","article-title":"Oxidative stress as a key feature of autoimmune thyroiditis: An update","volume":"45","author":"Ruggeri","year":"2020","journal-title":"Minerva Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12011-019-01963-5","article-title":"Trace Element Status and Hypothyroidism: A Systematic Review and Meta-analysis","volume":"197","author":"Talebi","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.1007\/s12011-020-02548-3","article-title":"Randomized Study of the Effects of Zinc, Vitamin A, and Magnesium Co-supplementation on Thyroid Function, Oxidative Stress, and hs-CRP in Patients with Hypothyroidism","volume":"199","author":"Rabbani","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1210\/clinem\/dgac473","article-title":"Thyroid, Diet, and Alternative Approaches","volume":"107","author":"Larsen","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7664641","DOI":"10.1155\/2021\/7664641","article-title":"Association of Polygenetic Risk Scores Related to Immunity and Inflammation with Hyperthyroidism Risk and Interactions between the Polygenetic Scores and Dietary Factors in a Large Cohort","volume":"2021","author":"Song","year":"2021","journal-title":"J. Thyroid. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fendo.2017.00057","article-title":"Genetics of Thyroid-Stimulating Hormone Receptor\u2014Relevance for Autoimmune Thyroid Disease","volume":"8","author":"Stefan","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.4049\/jimmunol.1500183","article-title":"Graves\u2019 Disease TSHR-Stimulating Antibodies (TSAbs) Induce the Activation of Immature Thymocytes: A Clue to the Riddle of TSAbs Generation?","volume":"194","author":"Colobran","year":"2015","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/nrendo.2015.27","article-title":"TSHR mutations and subclinical congenital hypothyroidism","volume":"11","author":"Schoenmakers","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cca.2019.07.031","article-title":"Mutation screening of the TSHR gene in 220 Chinese patients with congenital hypothyroidism","volume":"497","author":"Fang","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cca.2016.09.007","article-title":"Next-generation sequencing analysis of TSHR in 384 Chinese subclinical congenital hypothyroidism (CH) and CH patients","volume":"462","author":"Fu","year":"2016","journal-title":"Clin. Chim. Acta"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/17\/3850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:45:45Z","timestamp":1760129145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/17\/3850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,3]]},"references-count":55,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["nu15173850"],"URL":"https:\/\/doi.org\/10.3390\/nu15173850","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,3]]}}}