{"id":262,"date":"2024-01-08T17:00:13","date_gmt":"2024-01-08T17:00:13","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=f7b97583a597e336e07189c9d760a56f"},"modified":"2024-02-08T00:01:23","modified_gmt":"2024-02-08T00:01:23","slug":"iron-and-risk-of-dementia-mendelian-randomisation-analysis-in-uk-biobank","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2024\/01\/08\/iron-and-risk-of-dementia-mendelian-randomisation-analysis-in-uk-biobank\/","title":{"rendered":"Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank"},"content":{"rendered":"<sec><st>Background<\/st><p>Brain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter.<\/p><\/sec><sec><st>Methods<\/st><p>We analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer&rsquo;s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia.<\/p><\/sec><sec><st>Results<\/st><p>In Europeans, higher genetically predicted TSAT increased genetic liability to dementia (Odds Ratio [OR]: 1.15, 95% Confidence Intervals [CI] 1.04 to 1.26, p=0.0051), non-AD dementia (OR: 1.27, 95% CI 1.12 to 1.45, p=0.00018) and vascular dementia (OR: 1.37, 95% CI 1.12 to 1.69, p=0.0023), but not AD (OR: 1.00, 95% CI 0.86 to 1.15, p=0.97). Higher TSAT was also associated with increased risk of non-AD dementia in participants of African, but not South Asian groups. In survival analysis using a TSAT polygenic score, the effect was independent of apolipoprotein-E 4 genotype (with adjustment subdistribution Hazard Ratio: 1.74, 95% CI 1.33 to 2.28, p=0.00006). Genetically predicted TSAT was associated with lower grey matter volume in caudate, putamen and thalamus, and not in other areas of interest.<\/p><\/sec><sec><st>Discussion<\/st><p>Genetic evidence supports a causal relationship between higher TSAT and risk of clinically defined non-AD and vascular dementia, in European and African groups. This association appears to be independent of apolipoprotein-E 4.<\/p><\/sec>","protected":false},"excerpt":{"rendered":"<p>BackgroundBrain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey&#8230;<\/p>\n","protected":false},"author":1,"featured_media":461,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8,9],"tags":[],"class_list":["post-262","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-articulos","category-jmg-first","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/262","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=262"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/262\/revisions"}],"predecessor-version":[{"id":263,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/262\/revisions\/263"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media\/461"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=262"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=262"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=262"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}