{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:56:12Z","timestamp":1790794572069,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970651 92046018"],"award-info":[{"award-number":["31970651 92046018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    It remains unclear whether the observed heterogeneity in the burden of inflammatory bowel disease (IBD) across countries is associated with differences in population genetic structure. To address this problem, we performed a burden quantitative trait locus (bQTL) analysis, integrating epidemiological data (1990\u20132021) from the Global Burden of Disease (GBD) study with genotypes of 2\u00a0621\u00a0978 SNPs from 2414 unrelated individuals in the 1000 Genomes Project across 20 matched countries. We identified 1074 bQTLs of IBD, of which 384 were significantly associated with both the age\u2010standardized prevalence rate and age\u2010standardized incidence rate. rs7633471 (chr3:30698616:C&gt;A) showed the strongest effect: each increase in centi\u2010allele frequency (CAF) of the allele C was associated with a 10.00 decrease in age\u2010standardized prevalence rate and a 1.02 decrease in age\u2010standardized incidence rate. Pathway analysis revealed that bQTLs were primarily enriched in synaptic membrane, voltage\u2010gated potassium channel complex, and potassium channel complex. Through fine\u2010mapping, we further identified 800 putative causal variants for IBD, with significant findings located within genes related to the immune system (\n                    <jats:italic>IGSF21<\/jats:italic>\n                    and\n                    <jats:italic>CSMD2<\/jats:italic>\n                    ), inflammatory response (\n                    <jats:italic>SMPDL3B<\/jats:italic>\n                    and\n                    <jats:italic>AOAH<\/jats:italic>\n                    ), and intestinal cancers (\n                    <jats:italic>FHIT<\/jats:italic>\n                    and\n                    <jats:italic>CSMD2<\/jats:italic>\n                    ). Our study provides the first comprehensive characterization of the genetic architecture underlying the global burden of IBD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202519007","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Genetics With Epidemiological Measurements Identifies Burden QTLs of Inflammatory Bowel Disease across 20 Countries"],"prefix":"10.1002","author":[{"given":"Chen","family":"Sun","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxian","family":"Tao","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Faculty of Information Engineering and Automation Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Duan","sequence":"additional","affiliation":[{"name":"Central Laboratory The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanbo","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Mucosa The Second Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linna","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"She","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinduo","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Dong","sequence":"additional","affiliation":[{"name":"Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Tang","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital Zhejiang University School of Medicine  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Shang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-6554","authenticated-orcid":false,"given":"Yongshuai","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchao","family":"Lyu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586\u2010024\u201002556\u20106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3760"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384\u2010024\u201004711\u2010x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.12.025"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000003542"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)32448\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.150"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.04.042"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab248"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010019\u20100415\u20100"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izae081"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjv130"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102022\u2010065186"},{"issue":"1","key":"e_1_2_10_15_1","first-page":"17","article-title":"The Global, Regional, And National Burden Of Inflammatory Bowel Disease In 195 Countries And Territories, 1990\u20102017: A Systematic Analysis For The Global Burden Of Disease Study","volume":"2020","author":"Collaborators GBDIBD","year":"2017","journal-title":"The lancet Gastroenterology & hepatology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010020\u201000360\u2010x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advnut.2024.100219"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103498"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac269"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010023\u201001244\u2010w"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010024\u201001355\u2010y"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010025\u201000906\u20109"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3359"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14464"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"issue":"10","key":"e_1_2_10_26_1","first-page":"795","article-title":"Global, Regional, And National Burden Of Stroke And Its Risk Factors, 1990\u20102019: A Systematic Analysis For The Global Burden Of Disease Study 2019","volume":"2021","author":"Collaborators GBDS","year":"2019","journal-title":"The Lancet Neurology"},{"issue":"10100","key":"e_1_2_10_27_1","first-page":"1211","article-title":"Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived With disability for 328 diseases and injuries for 195 countries, 1990\u20102016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"390","year":"2016","journal-title":"Lancet"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010024\u201007083\u20103"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2024.106250"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194\u2010023\u201001619\u20109"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32989\u20107"},{"issue":"7","key":"e_1_2_10_32_1","first-page":"2015","article-title":"Global Trend of Breast Cancer Mortality Rate: A 25\u2010Year Study. Asian Pacific Journal of Cancer Prevention","volume":"20","author":"Azamjah N.","year":"2019","journal-title":"APJCP"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)30427\u20101"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001957\u20102"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889\u2010022\u201014042\u20107"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhealeco.2022.102714"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2024.342444"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3791\/60827"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010022\u201001286\u20107"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010023\u201001510\u2010y"},{"issue":"3","key":"e_1_2_10_41_1","article-title":"clusterProfiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu T.","year":"2021","journal-title":"Innovation"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5MB00663E"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385\u2010020\u201000368\u20101"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2025.108831"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i4.412"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1282431"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2387800"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwad026"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj1182"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09272-9"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202519007","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202519007","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202519007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:16:33Z","timestamp":1790792193000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202519007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":49,"alternative-id":["10.1002\/advs.202519007"],"URL":"https:\/\/doi.org\/10.1002\/advs.202519007","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2025-09-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e19007"}}