{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:36:13Z","timestamp":1772246173552,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-180615 Canadian Graduate Scholarships- Master\u2019s Award"],"award-info":[{"award-number":["PJT-180615 Canadian Graduate Scholarships- Master\u2019s Award"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Two genome-wide statistically significant (\n                    <jats:italic>p<\/jats:italic>\n                    value &amp;lt; 5 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) interaction effects and several suggestive (\n                    <jats:italic>p<\/jats:italic>\n                    value &amp;lt; 10\n                    <jats:sup>\u20135<\/jats:sup>\n                    ) interaction effects were found. These suggestive interaction effects were mapped to several genes including\n                    <jats:italic>HSD11B2<\/jats:italic>\n                    , associated with sex hormones, and\n                    <jats:italic>AGRP<\/jats:italic>\n                    , associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion:<\/jats:bold>\n                    By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2024.1411931","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:39:01Z","timestamp":1722386341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect modification by sex of genetic associations of vitamin C related metabolites in the Canadian Longitudinal study on aging"],"prefix":"10.3389","volume":"15","author":[{"given":"Rebecca","family":"Lelievre","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan","family":"Rakesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pirro G.","family":"Hysi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Little","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen E.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-H\u00e9l\u00e8ne","family":"Roy-Gagnon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1001\/archopht.119.10.1417","article-title":"A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8","volume":"119","year":"2001","journal-title":"Arch. 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