{"id":422,"date":"2018-06-05T00:45:03","date_gmt":"2018-06-05T00:45:03","guid":{"rendered":"http:\/\/www.altmann.eu\/research\/?p=422"},"modified":"2018-06-05T00:45:56","modified_gmt":"2018-06-05T00:45:56","slug":"paper-published-in-brain-2","status":"publish","type":"post","link":"http:\/\/www.altmann.eu\/research\/?p=422","title":{"rendered":"Paper published in Brain!"},"content":{"rendered":"<p>Marzia&#8217;s paper with the title <a href=\"https:\/\/doi.org\/10.1093\/brain\/awy141\"><em>&#8220;Genetic study of multimodal imaging Alzheimer\u2019s disease progression score implicates novel loci&#8221;<\/em> <\/a>has been published in Brain. Congrats!<\/p>\n<p><script type=\"text\/javascript\" src=\"https:\/\/d1bxh8uas1mnw7.cloudfront.net\/assets\/embed.js\"><\/script><\/p>\n<div class=\"altmetric-embed\" data-badge-type=\"donut\" data-altmetric-id=\"43079032\"><\/div>\n<p>Abstract:<br \/>\nIdentifying genetic risk factors underpinning different aspects of Alzheimer\u2019s disease has the potential to provide important insights into pathogenesis. Moving away from simple case-control definitions, there is considerable interest in using quantitative endophenotypes, such as those derived from imaging as outcome measures. Previous genome-wide association studies of imaging-derived biomarkers in sporadic late-onset Alzheimer\u2019s disease focused only on phenotypes derived from single imaging modalities. In contrast, we computed a novel multi-modal neuroimaging phenotype comprising cortical amyloid burden and bilateral hippocampal volume. Both imaging biomarkers were used as input to a disease progression modelling algorithm, which estimates the biomarkers\u2019 long-term evolution curves from population-based longitudinal data. Among other parameters, the algorithm computes the shift in time required to optimally align a subjects\u2019 biomarker trajectories with these population curves. This time shift serves as a disease progression score and it was used as a quantitative trait in a discovery genome-wide association study with\u00a0<em>n<\/em>\u00a0= 944 subjects from the Alzheimer\u2019s Disease Neuroimaging Initiative database diagnosed as Alzheimer\u2019s disease, mild cognitive impairment or healthy at the time of imaging. We identified a genome-wide significant locus implicating\u00a0<em>LCORL<\/em>\u00a0(rs6850306, chromosome 4;\u00a0<em>P<\/em>\u00a0= 1.03 \u00d7 10<sup>\u22128<\/sup>). The top variant rs6850306 was found to act as an expression quantitative trait locus for\u00a0<em>LCORL<\/em>\u00a0in brain tissue. The clinical role of rs6850306 in conversion from healthy ageing to mild cognitive impairment or Alzheimer\u2019s disease was further validated in an independent cohort comprising healthy, older subjects from the National Alzheimer\u2019s Coordinating Center database. Specifically, possession of a minor allele at rs6850306 was protective against conversion from mild cognitive impairment to Alzheimer\u2019s disease in the National Alzheimer\u2019s Coordinating Center cohort (hazard ratio = 0.593, 95% confidence interval = 0.387\u20130.907,\u00a0<em>n<\/em>\u00a0= 911,\u00a0<em>P<\/em><sub>Bonf<\/sub>\u00a0= 0.032), in keeping with the negative direction of effect reported in the genome-wide association study (\u03b2<sub>disease progression score<\/sub>\u00a0= \u22120.07 \u00b1 0.01). The implicated locus is linked to genes with known connections to Alzheimer\u2019s disease pathophysiology and other neurodegenerative diseases. Using multimodal imaging phenotypes in association studies may assist in unveiling the genetic drivers of the onset and progression of complex diseases.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Marzia&#8217;s paper with the title &#8220;Genetic study of multimodal imaging Alzheimer\u2019s disease progression score implicates novel loci&#8221; has been published in Brain. Congrats! Abstract: Identifying genetic risk factors underpinning different aspects of Alzheimer\u2019s disease has the potential to provide important insights into pathogenesis. Moving away from simple case-control definitions, there is considerable interest in using [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-422","post","type-post","status-publish","format-standard","hentry","category-research","entry"],"_links":{"self":[{"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=\/wp\/v2\/posts\/422","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=422"}],"version-history":[{"count":2,"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=\/wp\/v2\/posts\/422\/revisions"}],"predecessor-version":[{"id":424,"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=\/wp\/v2\/posts\/422\/revisions\/424"}],"wp:attachment":[{"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=422"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=422"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www.altmann.eu\/research\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=422"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}