{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T13:44:03Z","timestamp":1777124643008,"version":"3.51.4"},"reference-count":146,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH116527"],"award-info":[{"award-number":["MH116527"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS110791"],"award-info":[{"award-number":["NS110791"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG082938"],"award-info":[{"award-number":["RF1AG082938"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mounting evidence suggests considerable diversity in brain aging trajectories, primarily arising from the complex interplay between age, genetic, and environmental risk factors, leading to distinct patterns of micro- and macro-cerebral aging. The underlying mechanisms of such effects still remain unclear. We conducted a comprehensive association analysis between cerebral structural measures and prevalent risk factors, using data from 36,969 UK Biobank subjects aged 44\u201381. Participants were assessed for brain volume, white matter diffusivity, Apolipoprotein E (APOE) genotypes, polygenic risk scores, lifestyles, and socioeconomic status. We examined genetic and environmental effects and their interactions with age and sex, and identified 726 signals, with education, alcohol, and smoking affecting most brain regions. Our analysis revealed negative age-APOE-\u03b54 and positive age-APOE-\u03b52 interaction effects, respectively, especially in females on the volume of amygdala, positive age-sex-APOE-\u03b54 interaction on the cerebellar volume, positive age-excessive-alcohol interaction effect on the mean diffusivity of the splenium of the corpus callosum, positive age-healthy-diet interaction effect on the paracentral volume, and negative APOE-\u03b54-moderate-alcohol interaction effects on the axial diffusivity of the superior fronto-occipital fasciculus. These findings highlight the need of considering age, sex, genetic, and environmental joint effects in elucidating normal or abnormal brain aging.<\/jats:p>","DOI":"10.1093\/cercor\/bhad472","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T17:26:32Z","timestamp":1700501192000},"source":"Crossref","is-referenced-by-count":10,"title":["The interaction effects of age,\n                    <i>APOE<\/i>\n                    and common environmental risk factors on human brain structure"],"prefix":"10.1093","volume":"34","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill NC 27514 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology , School of Medicine, , 101 Manning Drive, Chapel Hill, NC 27514 , United States"},{"name":"University of North Carolina at Chapel Hill , School of Medicine, , 101 Manning Drive, Chapel Hill, NC 27514 , United States"},{"name":"Biomedical Research Imaging Center , School of Medicine, , 125 Mason Farm Road, Chapel Hill, NC 27599 , United States"},{"name":"University of North Carolina at Chapel Hill , School of Medicine, , 125 Mason Farm Road, Chapel Hill, NC 27599 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Statistics and Data Science , The Wharton School, , 265 South 37th Street, 3rd & 4th Floors, Philadelphia, PA 19104-1686 , United States"},{"name":"University of Pennsylvania , The Wharton School, , 265 South 37th Street, 3rd & 4th Floors, Philadelphia, PA 19104-1686 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang University School of Medicine , 866 Yuhangtang Rd, Hangzhou 310058 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changzheng","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang University School of Medicine , 866 Yuhangtang Rd, Hangzhou 310058 , China"},{"name":"Department of Nutrition, Harvard T H Chan School of Public Health , 665 Huntington Avenue Boston, MA, 02115 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwenn A","family":"Garden","sequence":"additional","affiliation":[{"name":"Department of Neurology , School of Medicine, , 170 Manning Drive Chapel Hill, NC 27599-7025 , United States"},{"name":"University of North Carolina at Chapel Hill , School of Medicine, , 170 Manning Drive Chapel Hill, NC 27599-7025 , United 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