{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:11:15Z","timestamp":1787944275490,"version":"build-2784847793"},"reference-count":32,"publisher":"Korean Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2019-NI-097-02"],"award-info":[{"award-number":["2019-NI-097-02"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2022-NI-065-01"],"award-info":[{"award-number":["2022-NI-065-01"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2022-NI-067-01"],"award-info":[{"award-number":["2022-NI-067-01"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>Background: This study aimed to investigate the modifying effects of rare genetic variants on the risk of type 2 diabetes mellitus (T2DM) in the context of common genetic and lifestyle factors.Methods: We conducted a comprehensive analysis of genetic and lifestyle factors associated with T2DM in a cohort of 146,284 Korean individuals. Among them, 4,603 individuals developed T2DM during the follow-up period of up to 17 years. We calculated a polygenic risk score (PRS) for T2DM and identified carriers of the rare allele I349F at SLC30A8. A Healthy Lifestyle Score (HLS) was also derived from physical activity, obesity, smoking, diet, and sodium intake levels. Using Cox proportional hazards models, we analyzed how PRS, HLS, and I349F influenced T2DM incidence.Results: Results showed that high PRS and poor lifestyle were associated with increased risk. Remarkably, I349F carriers exhibited a lower T2DM prevalence (5.7% compared to 11.7% in non-carriers) and reduced the impact of high PRS from 23.18% to 12.70%. This trend was consistent across different HLS categories, with I349F carriers displaying a lower risk of T2DM.Conclusion: The integration of common and rare genetic variants with lifestyle factors enhanced T2DM predictability in the Korean population. Our findings highlight the critical role of rare genetic variants in risk assessments and suggest that standard PRS and HLS metrics alone may be inadequate for predicting T2DM risk among carriers of such variants.<\/jats:p>","DOI":"10.4093\/dmj.2024.0830","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T08:07:47Z","timestamp":1755072467000},"page":"385-395","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SLC30A8 Rare Variant Modify Contribution of Common Genetic and Lifestyle Factors toward Type 2 Diabetes Mellitus"],"prefix":"10.4093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8744-0487","authenticated-orcid":true,"given":"Hye-Mi","family":"Jang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Yeong","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Seul","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3562-2654","authenticated-orcid":true,"given":"Bong-Jo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-4437","authenticated-orcid":true,"given":"Young Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71908-9"},{"key":"ref2","first-page":"1505","volume-title":"Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps","author":"Mahajan","year":"2018"},{"key":"ref3","first-page":"240","volume-title":"Identification of type 2 diabetes loci in 433,540 East Asian individuals","author":"Spracklen","year":"2020"},{"key":"ref4","first-page":"560","volume-title":"Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation","author":"Mahajan","year":"2022"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0183-z"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0018-x"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34163-2"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.03.003"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1605086"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.1717"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05140-5"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqz310"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv316"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37832-9"},{"key":"ref15","first-page":"68","volume-title":"A global reference for human genetic variation","author":"Auton","year":"2015"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1530\/ey.17.14.3"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3571"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007\/s13258-020-00982-0"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09718-5"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0332-4"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.4162\/nrp.2020.14.5.501"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2019-002028"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.007"},{"key":"ref26","volume-title":"","author":"Therneau","year":"2000"},{"key":"ref27","first-page":"680","volume-title":"Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis","author":"Vujkovic","year":"2020"},{"key":"ref28","first-page":"e1001647","volume-title":"Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study","author":"Langenberg","year":"2014"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0322-9"},{"key":"ref30","first-page":"732","volume-title":"The sequences of 150,119 genomes in the UK Biobank","author":"Halldorsson","year":"2022"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.2337\/dbi20-0001"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.151"}],"container-title":["Diabetes &amp; 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