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The life cycles of the tick vectors and spirochete pathogen are highly sensitive to climate, but determining the impact of climate change on Lyme disease burden has been challenging due to the complex ecology of the disease and the presence of multiple, interacting drivers of transmission. Here we incorporated 18\u00a0years of annual, county\u2010level Lyme disease case data in a panel data statistical model to investigate prior effects of climate variation on disease incidence while controlling for other putative drivers. We then used these climate\u2013disease relationships to project Lyme disease cases using CMIP5 global climate models and two potential climate scenarios (RCP4.5 and RCP8.5). We find that interannual variation in Lyme disease incidence is associated with climate variation in all US regions encompassing the range of the primary vector species. In all regions, the climate predictors explained less of the variation in Lyme disease incidence than unobserved county\u2010level heterogeneity, but the strongest climate\u2013disease association detected was between warming annual temperatures and increasing incidence in the Northeast. Lyme disease projections indicate that cases in the Northeast will increase significantly by 2050 (23,619\u00a0\u00b1\u00a021,607 additional cases), but only under RCP8.5, and with large uncertainty around this projected increase. Significant case changes are not projected for any other region under either climate scenario. The results demonstrate a regionally variable and nuanced relationship between climate change and Lyme disease, indicating possible nonlinear responses of vector ticks and transmission dynamics to projected climate change. Moreover, our results highlight the need for improved preparedness and public health interventions in endemic regions to minimize the impact of further climate change\u2010induced increases in Lyme disease burden.<\/jats:p>","DOI":"10.1111\/gcb.15435","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T21:32:38Z","timestamp":1604525558000},"page":"738-754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Impact of prior and projected climate change on US Lyme disease incidence"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-8675","authenticated-orcid":false,"given":"Lisa I.","family":"Couper","sequence":"first","affiliation":[{"name":"Department of Biology Stanford University Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0172-7749","authenticated-orcid":false,"given":"Andrew J.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Earth Research Institute University of California Santa Barbara CA USA"},{"name":"Bren School of Environmental Science and Management University of California Santa Barbara CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A.","family":"Mordecai","sequence":"additional","affiliation":[{"name":"Department of Biology Stanford University Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116767"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-306-47630-3_15"},{"key":"e_1_2_9_4_1","first-page":"916","article-title":"Risk of Lyme disease: Perceptions of residents of a Lone Star tick\u2010infested community","volume":"79","author":"Armstrong P. 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