{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:31:48Z","timestamp":1785411108700,"version":"3.56.0"},"reference-count":43,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ERC Starting grant","award":["948207"],"award-info":[{"award-number":["948207"]}]},{"DOI":"10.13039\/501100006209","name":"Radboud Universitair Medisch Centrum","doi-asserted-by":"publisher","award":["Hypatia Grant 2018"],"award-info":[{"award-number":["Hypatia Grant 2018"]}],"id":[{"id":"10.13039\/501100006209","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERC advanced grant","award":["833247"],"award-info":[{"award-number":["833247"]}]},{"name":"the Netherlands Association of Scientific Reasearch","award":["Spinoza grant"],"award-info":[{"award-number":["Spinoza grant"]}]},{"name":"the Netherlands Organisation for Scientific Research","award":["Perspectief Biomarker Development Center Research Programme"],"award-info":[{"award-number":["Perspectief Biomarker Development Center Research Programme"]}]},{"DOI":"10.13039\/501100001648","name":"European Foundation for the Study of Diabetes","doi-asserted-by":"publisher","award":["AZ Macrovascular Programme 2015"],"award-info":[{"award-number":["AZ Macrovascular Programme 2015"]}],"id":[{"id":"10.13039\/501100001648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201706040081"],"award-info":[{"award-number":["201706040081"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,5,16]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The large inter-individual variability in immune-cell composition and function determines immune responses in general and susceptibility o immune-mediated diseases in particular. While much has been learned about the genetic variants relevant for type 1 diabetes (T1D), the pathophysiological mechanisms through which these variations exert their effects remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Blood samples were collected from 243 patients with T1D of Dutch descent. We applied genetic association analysis on &gt;200 immune-cell traits and &gt;100 cytokine production profiles in response to stimuli measured to identify genetic determinants of immune function, and compared the results obtained in T1D to healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Genetic variants that determine susceptibility to T1D significantly affect T cell composition. Specifically, the CCR5+ regulatory T cells associate with T1D through the CCR region, suggesting a shared genetic regulation. Genome-wide quantitative trait loci (QTLs) mapping analysis of immune traits revealed 15 genetic loci that influence immune responses in T1D, including 12 that have never been reported in healthy population studies, implying a disease-specific genetic regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study provides new insights into the genetic factors that affect immunological responses in T1D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>This work was supported by an ERC starting grant (no. 948207) and a Radboud University Medical Centre Hypatia grant (2018) to YL and an ERC advanced grant (no. 833247) and a Spinoza grant of the Netherlands Association for Scientific Research to MGN CT received funding from the Perspectief Biomarker Development Center Research Programme, which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO). AJ was funded by a grant from the European Foundation for the Study of Diabetes (EFSD\/AZ Macrovascular Programme 2015). XC was supported by the China Scholarship Council (201706040081).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.73709","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T04:15:41Z","timestamp":1653365741000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73709","source":"Crossref","is-referenced-by-count":8,"title":["A genome-wide functional genomics approach uncovers genetic determinants of immune phenotypes in type 1 diabetes"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-2912","authenticated-orcid":true,"given":"Xiaojing","family":"Chu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012p63287","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, University of Groningen, University Medical Center Groningen","place":["Groningen, 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