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Genome\u2010wide association studies (GWAS) have identified plausible loci correlated with peripheral levels of Fe. Systemic organs and the brain share several Fe regulatory proteins but there likely exist different homeostatic pathways. We performed the first GWAS of inductively coupled plasma mass spectrometry measures of postmortem brain Fe from 635 Rush Memory and Aging Project (MAP) participants. Sixteen single nucleotide polymorphisms (SNPs) associated with Fe in at least one of four brain regions were measured (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). Promising SNPs (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22126<\/jats:sup>\n                    ) were followed up for replication in published GWAS of blood, spleen, and brain imaging Fe traits and mapped to candidate genes for targeted cortical transcriptomic and epigenetic analysis of postmortem Fe in MAP. Results for SNPs previously associated with other Fe traits were also examined. Ninety\u2010eight SNPs associated with postmortem brain Fe were at least nominally (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) associated with one or more related Fe traits. Most novel loci identified had no direct links to Fe regulatory pathways but rather endoplasmic reticulum\u2010Golgi trafficking (\n                    <jats:italic>SORL1, SORCS2, MARCH1, CLTC<\/jats:italic>\n                    ), heparan sulfate (\n                    <jats:italic>HS3ST4, HS3ST1<\/jats:italic>\n                    ), and coenzyme A (\n                    <jats:italic>SLC5A6, PANK3<\/jats:italic>\n                    ); supported by nearest gene function and omic analyses. We replicated (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) several previously published Fe loci mapping to candidate genes in cellular and systemic Fe regulation. Finally, novel loci (\n                    <jats:italic>BMAL, COQ5, SLC25A11<\/jats:italic>\n                    ) and replication of prior loci (\n                    <jats:italic>PINK1, PPIF, LONP1<\/jats:italic>\n                    ) lend support to the role of circadian rhythms and mitochondria function in Fe regulation more generally. In summary, we provide support for novel loci linked to pathways that may have greater relevance to brain Fe accumulation; some of which are implicated in neurodegeneration. However, replication of a subset of prior loci for blood Fe suggests that genetic determinants or biological pathways underlying Fe accumulation in the brain are not completely distinct from those of Fe circulating in the periphery.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16309-fig-0003-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16309","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T07:54:04Z","timestamp":1738914844000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Markers of Postmortem Brain Iron"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0699-1664","authenticated-orcid":false,"given":"Marilyn C.","family":"Cornelis","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Fazlollahi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Royal Melbourne Hospital University of Melbourne  Melbourne Victoria Australia"},{"name":"Queensland Brain Institute The University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3479-2427","authenticated-orcid":false,"given":"Scott","family":"Ayton","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Melbourne Victoria Australia"},{"name":"Florey Department of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria 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