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Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking\/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco\/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The RR of LADA was elevated in high IR-GRS heavy smokers (\u226515 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (\u226515 box\/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (P = 0.003; P = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc22-2284","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T17:01:25Z","timestamp":1677862885000},"page":"1028-1036","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":9,"title":["Incidence of LADA and Type 2 Diabetes in Relation to Tobacco Use and Genetic Susceptibility to Type 2 Diabetes and Related Traits: Findings From a Swedish Case-Control Study and the Norwegian HUNT Study"],"prefix":"10.2337","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6009-8738","authenticated-orcid":false,"given":"Jessica","family":"Edstorp","sequence":"first","affiliation":[{"name":"1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6513-2384","authenticated-orcid":false,"given":"Emma","family":"Ahlqvist","sequence":"additional","affiliation":[{"name":"2Department of Clinical Sciences in Malm\u00f6, Lund University Diabetes Centre, Lund University, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[{"name":"1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"3Center for Occupational and Environmental Medicine, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Mansour Aly","sequence":"additional","affiliation":[{"name":"2Department of Clinical Sciences in Malm\u00f6, Lund University Diabetes Centre, Lund University, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-022X","authenticated-orcid":false,"given":"Valdemar","family":"Grill","sequence":"additional","affiliation":[{"name":"4Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8597-993X","authenticated-orcid":false,"given":"Bahareh","family":"Rasouli","sequence":"additional","affiliation":[{"name":"1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"5Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-2386","authenticated-orcid":false,"given":"Elin P.","family":"S\u00f8rgjerd","sequence":"additional","affiliation":[{"name":"6HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway"},{"name":"7Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8306-6202","authenticated-orcid":false,"given":"Tiinamaija","family":"Tuomi","sequence":"additional","affiliation":[{"name":"2Department of Clinical Sciences in Malm\u00f6, Lund University Diabetes Centre, Lund University, Malm\u00f6, Sweden"},{"name":"8Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland"},{"name":"9Division of Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland"},{"name":"10Research Program for Diabetes and Obesity, University of Helsinki, Helsinki, Finland"},{"name":"11Folkh\u00e4lsan Research Center, Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f8rn O.","family":"\u00c5svold","sequence":"additional","affiliation":[{"name":"6HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway"},{"name":"7Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim, Norway"},{"name":"12K.G. 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