{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:24:13Z","timestamp":1777875853255,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) plays a major role as a \u201cdanger signal\u201d on stressed cells to promote removal of the latter by NKG2D-expressing cytotoxic lymphocytes. NKG2DL expression has been found in peripheral immune cells as well, such as in macrophages; however, the effect of this expression is yet to be determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We determined instrumental variables (IVs;\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      &lt;0.01 in linkage disequilibrium), explaining the major variance in major histocompatibility complex class I chain-related protein A (MICA) and B (MICB) gene expression levels from the expression-quantitative trait locus (eQTL) of NKG2DLs based on the RNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from 381 Japanese. Simultaneously, the target outcomes were filtered by PheWAS from 58 health risks, using a community-based cohort study composed of 44,739 Japanese residents. Finally, we estimated the causal effect of gene expression levels on the outcomes using the Mendelian randomization approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We determined nine and four IVs, explaining 87.6% and 33.0% of\n                      <jats:italic toggle=\"yes\">MICA<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MICB<\/jats:italic>\n                      gene expression levels, respectively. In the association test, we identified 10 or 13 significant outcomes associated with the\n                      <jats:italic toggle=\"yes\">MICA<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">MICB<\/jats:italic>\n                      eQTLs, respectively, as well as the causal effect of MICA expression on Graves' disease (GD) (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20094.2\u2009\u00d7\u200910\n                      <jats:sup>\u22123<\/jats:sup>\n                      ; odds ratio per 1 S.D. difference in the expression: 0.983 [confidence interval: 0.971\u20130.995]), using the weighted median estimator, without significant pleiotropy (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&gt;\u20090.05), and the results were consistent across the sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our study provide novel evidence associating NKG2DL expression with GD, an autoimmune thyroiditis; direction of the effect indicated the immunoregulatory role of MICA expression in PBMCs, suggesting the importance of further functional assays in inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2021.0417","type":"journal-article","created":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T01:22:19Z","timestamp":1638580939000},"page":"188-195","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Low\n                    <i>MICA<\/i>\n                    Gene Expression Confers an Increased Risk of Graves' Disease: A Mendelian Randomization Study"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1607-9759","authenticated-orcid":false,"given":"Yoichi","family":"Sutoh","sequence":"first","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Komaki","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiki","family":"Yamaji","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiori","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan."},{"name":"Division of Cancer Medicine, Jikei University School of Medicine, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoko","family":"Katagiri","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norie","family":"Sawada","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanako","family":"Ono","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Ohmomo","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Hachiya","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yayoi","family":"Otsuka-Yamasaki","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Takashima","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So","family":"Umekage","sequence":"additional","affiliation":[{"name":"Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoki","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, 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