{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T23:42:56Z","timestamp":1777765376132,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK202302003"],"award-info":[{"award-number":["GK202302003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31370129"],"award-info":[{"award-number":["31370129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Addict"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>\n                      Numerous genome\u2010wide association studies suggest that rs1051730 is significantly associated with nicotine dependence and further lung cancer in Caucasian. Since rs1051730 is a synonymous variant at\n                      <jats:italic>CHRNA3<\/jats:italic>\n                      (cholinergic receptor nicotinic alpha 3 subunit), it might be hypothesized that the causal variant might be other SNP(s) in strong linkage disequilibrium (LD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LD analysis and functional genomics work, including chromosome conformation capture (3C), luciferase assay, and chromatin immunoprecipitation (ChIP), were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Allele\u2010specific expression indicates an overexpression of C allele than T at rs1051730 in lung tissues, thus verifying the hypothesis. Through LD analysis for 1000 genomes project data, 17 genetic variants are identified in strong LD with rs1051730. 3C indicates that two restrictive segments, chr15:78845145\u201078852557 and chr15:78867861\u201078872762, display high interaction efficiency with\n                      <jats:italic>CHRNA3<\/jats:italic>\n                      promoter and contain two SNPs in core haplotype, rs72740964 and rs2036527, respectively. Luciferase assay suggests that only rs2036527 can alter enhancer activity. Further 3C indicates that\n                      <jats:italic>CHRNA5<\/jats:italic>\n                      (cholinergic receptor nicotinic alpha 5 subunit) is an additional target of the enhancer containing rs2036527, which is verified by expression quantitative trait locus analysis. By ChIP, the related transcription factor, FOXA2 (forkhead box A2), is identified and their interaction is evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusions<\/jats:title>\n                    <jats:p>\n                      rs2036527 is the\n                      <jats:italic>cis<\/jats:italic>\n                      \u2010regulatory variant for\n                      <jats:italic>CHRNA3<\/jats:italic>\n                      and\n                      <jats:italic>CHRNA5<\/jats:italic>\n                      , which can further influence nicotine dependence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Scientific Significance<\/jats:title>\n                    <jats:p>This is the first report to indicate that rs2036527 genotype might be a better marker to predict the probability of developing nicotine dependence and that FOXA2, CHRNA5, and CHRNA3 might be treatment targets for nicotine dependence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ajad.70074","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T06:34:17Z","timestamp":1754289257000},"page":"379-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of rs2036527 as a\n                    <i>cis<\/i>\n                    \u2010regulatory variant for\n                    <i>CHRNA3<\/i>\n                    and\n                    <i>CHRNA5<\/i>\n                    by allele\u2010specific expression and implications for nicotine dependence and lung cancer"],"prefix":"10.1111","volume":"35","author":[{"given":"Tao","family":"Peng","sequence":"first","affiliation":[{"name":"College of Life Sciences Shaanxi Normal University Xi'an Shaanxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Qian","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Life Sciences Shaanxi Normal University Xi'an Shaanxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Life Sciences Shaanxi Normal University Xi'an Shaanxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Yan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences Shaanxi Normal University Xi'an Shaanxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi\u2010Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Sciences Shaanxi Normal University Xi'an Shaanxi P.R. 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