{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:53:14Z","timestamp":1777661594942,"version":"3.51.4"},"reference-count":59,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Central Government Guidance for Local Science and Technology Development Fund Projects","award":["ZYYD2025ZY14"],"award-info":[{"award-number":["ZYYD2025ZY14"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["High Altitude Medicine &amp; Biology"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>\n                    Zhang, Xingkai, Liang He, Kai Li, Wen Li, Li Wang, Ling Chen, and Qinghai Shi. Causal relationships between high-altitude adaptation, metabolic traits, and tumors: insights from Mendelian randomization.\n                    <jats:italic toggle=\"yes\">High Alt Med Biol.<\/jats:italic>\n                    27:23\u201332, 2026.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Background and Objectives:<\/jats:title>\n                    <jats:p>Previous studies suggest that high-altitude adaptation (HAA) and metabolic traits in high-altitude populations correlate with tumor risk, but causal mechanisms remain unclear. This Mendelian randomization (MR) study investigated genetic links between HAA, metabolic traits, and tumor susceptibility while exploring potential mediation effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Genome-wide association studies data for HAA, metabolic traits, and tumors were sourced from public databases. Inverse variance weighting served as the primary analytical method, supplemented by weighted mode, MR-Egger, and weighted median. Sensitivity analyses and two-step MR (TSMR) assessed robustness and mediation pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified a potential association between HAA and a decreased risk of pancreatic cancer (odds ratio [OR] = 8.94e-8,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.011) and cervical cancer (OR = 8.04e-6,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.005). In contrast, HAA showed a potential link to an increased risk of esophageal cancer (OR = 3230.25,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.03) and hepatocellular carcinoma (OR = 2080.07,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.015). Several metabolic traits, particularly platelet-related indices, were identified as potentially associated with tumorigenesis. However, although possible mediating pathways were suggested, no metabolic trait demonstrated a statistically significant mediating effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings highlight HAA\u2019s complex role in tumor susceptibility and provide a genetic framework for understanding tumor disparities in high-altitude regions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15578682251382795","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T14:31:36Z","timestamp":1758810696000},"page":"23-32","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Relationships Between High-Altitude Adaptation, Metabolic Traits, and Tumors: Insights from Mendelian Randomization"],"prefix":"10.1177","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5389-8478","authenticated-orcid":false,"given":"Xingkai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Graduate School, Xinjiang Medical University, Urumqi, China."},{"name":"Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"He","sequence":"additional","affiliation":[{"name":"Department of General Surgery, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.04.007"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icj004"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2634"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.250167.114"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2016.06.018"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy258"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.842800"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.189365.112"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1667\/rr3333.1"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-01792-0"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01727-1"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121337"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2013.01.017"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.909474"},{"issue":"3","key":"e_1_3_4_19_1","first-page":"155","article-title":"GCH1 plays a role in the high-altitude adaptation of Tibetans","volume":"38","author":"Guo YB","year":"2017","unstructured":"Guo YB, , He YX, , Cui CY, et al. 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