{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:18:43Z","timestamp":1791980323498,"version":"4.4.0"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG040370"],"award-info":[{"award-number":["R01AG040370"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The\n                      <jats:italic>TOMM40<\/jats:italic>\n                      poly\u2010T is a polymorphism in intron 6 of the\n                      <jats:italic>TOMM40<\/jats:italic>\n                      gene, which is adjacent to and in linkage disequilibrium with\n                      <jats:italic>APOE<\/jats:italic>\n                      . Roses et\u00a0al. identified the association between the length of\n                      <jats:italic>TOMM40<\/jats:italic>\n                      poly\u2010T with the risk and age of onset of late\u2010onset Alzheimer's disease (LOAD). Following the original discovery, additional studies found associations between the\n                      <jats:italic>TOMM40<\/jats:italic>\n                      poly\u2010T and LOAD\u2010related phenotypes independent of\n                      <jats:italic>APOE<\/jats:italic>\n                      genotypes, while others did not replicate these associations. Furthermore, the identity of the\n                      <jats:italic>TOMM40<\/jats:italic>\n                      poly\u2010T risk allele has been controversial between different LOAD\u2010related phenotypes. Here, we propose a framework to address the conflicting findings with respect to the\n                      <jats:italic>TOMM40<\/jats:italic>\n                      poly\u2010T allele associations with LOAD phenotypes and their functional effects. The framework is used to interpret previous studies as means to gain insights regarding the nature of the risk allele, very long versus short. We suggest that the identity of the\n                      <jats:italic>TOMM40<\/jats:italic>\n                      poly\u2010T risk allele depends on the phenotype being evaluated, the ages of the study subjects at the time of assessment, and the context of the\n                      <jats:italic>APOE<\/jats:italic>\n                      genotypes. In concluding remarks, we outline future studies that will inform the mechanistic interpretation of the genetic data.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2018.01.015","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T00:33:21Z","timestamp":1520469201000},"page":"692-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["The effects of the\n                    <i>TOMM40<\/i>\n                    poly\u2010T alleles on Alzheimer's disease phenotypes"],"prefix":"10.1002","volume":"14","author":[{"given":"Ornit","family":"Chiba\u2010Falek","sequence":"first","affiliation":[{"name":"Department of Neurology Duke University Medical Center  Durham NC USA"},{"name":"Center for Genomic and Computational Biology Duke University Medical Center  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K.","family":"Gottschalk","sequence":"additional","affiliation":[{"name":"Department of Neurology Duke University Medical Center  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Department of Neurology Duke University Medical Center  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,7]]},"reference":[{"key":"e_1_2_3_2_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families","volume":"261","author":"Corder EH","year":"1993","journal-title":"Sci (New York, NY)"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(07)00414-2"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9649"},{"key":"e_1_2_3_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.440"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.439"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1212"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.135"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.45"},{"key":"e_1_2_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.574"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_3_13_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0419"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.123"},{"key":"e_1_2_3_15_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-101764"},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1329"},{"key":"e_1_2_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01615.x"},{"key":"e_1_2_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0189-9"},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.1.59"},{"key":"e_1_2_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.9.1434"},{"key":"e_1_2_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2007.02.002"},{"key":"e_1_2_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2009.69"},{"key":"e_1_2_3_23_2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.jalz.2012.06.009","article-title":"TOMM40 intron 6 poly\u2010T length, age at onset, and neuropathology of AD in individuals with APOE epsilon3\/epsilon3. 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