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"https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Huisman", "given": "Martijn", "initials": "M"}, {"family": "Andreassen", "given": "Ole A", "initials": "OA", "orcid": "0000-0002-4461-3568", "researcher": {"href": "https://publications.scilifelab.se/researcher/56f384e8e2fd4a7383c7b26e88a828b2.json"}}, {"family": "Posthuma", "given": "Danielle", "initials": "D"}, {"family": "Clarim\u00f3n", "given": "Jordi", "initials": "J"}, {"family": "Boada", "given": "Merc\u00e8", "initials": "M", "orcid": "0000-0003-2617-3009", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8d00c33569e41b481cf5cdc99cd96e9.json"}}, {"family": "van der Flier", "given": "Wiesje M", "initials": "WM", "orcid": "0000-0001-8766-6224", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b32776a9e524f299765506b6dbe9768.json"}}, {"family": "Ramirez", "given": "Alfredo", "initials": "A", "orcid": "0000-0003-4991-763X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8995a57e82f4f479ab8251175aeb8d6.json"}}, {"family": "Lambert", "given": "Jean-Charles", "initials": "JC", "orcid": "0000-0003-0829-7817", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0ec452344144906b7e8be95eb8c62d6.json"}}, {"family": "van der Lee", "given": "Sven J", "initials": "SJ", "orcid": "0000-0003-1606-8643", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a34a1b7b98b4360b48dafe3f0d5dcb2.json"}}, {"family": "Ruiz", "given": "Agust\u00edn", "initials": "A", "orcid": "0000-0003-2633-2495", "researcher": {"href": "https://publications.scilifelab.se/researcher/33a263bd6bd24ca897c988d4fcbcaca1.json"}}], "type": "journal article", "published": "2021-06-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "3417"}, "abstract": "Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE \u025b4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.", "doi": "10.1038/s41467-021-22491-8", "pmid": "34099642", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8184987"}, {"db": "pii", "key": "10.1038/s41467-021-22491-8"}], "notes": [], "created": "2021-08-19T13:41:32.762Z", "modified": "2023-06-20T15:56:47.699Z"}, {"entity": "publication", "iuid": "7fe0a03b3cf040bc9efcd73174997a3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7fe0a03b3cf040bc9efcd73174997a3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7fe0a03b3cf040bc9efcd73174997a3d"}}, "title": "Genetic architecture of subcortical brain structures in 38,851 individuals.", "authors": [{"family": "Satizabal", "given": "Claudia L", "initials": "CL", "orcid": "0000-0002-1115-4430", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fef87b562c74168ba8b9acbc9048eb9.json"}}, {"family": "Adams", "given": "Hieab H H", "initials": "HHH", "orcid": "0000-0003-3687-2508", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab5c4744d60d4290a3a8a6b80c107f42.json"}}, {"family": "Hibar", "given": "Derrek P", "initials": "DP"}, {"family": "White", "given": "Charles C", "initials": "CC"}, {"family": "Knol", "given": "Maria J", "initials": "MJ", "orcid": "0000-0002-3597-1531", "researcher": {"href": "https://publications.scilifelab.se/researcher/0edb736bd840429bbb57ecd1b2924561.json"}}, {"family": "Stein", "given": "Jason L", "initials": "JL"}, {"family": "Scholz", "given": "Markus", "initials": "M", "orcid": "0000-0002-4059-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d7b0e2dcdb4361b54016cb1550c5fe.json"}}, {"family": "Sargurupremraj", "given": 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"initials": "CA"}, {"family": "DeStefano", "given": "Anita L", "initials": "AL"}, {"family": "Heslenfeld", "given": "Dirk J", "initials": "DJ"}, {"family": "Weiner", "given": "Michael W", "initials": "MW"}, {"family": "Walter", "given": "Henrik", "initials": "H", "orcid": "0000-0002-9403-6121", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fb8400c66af486bae4c0d8b56c38316.json"}}, {"family": "Hoekstra", "given": "Pieter J", "initials": "PJ"}, {"family": "Nyquist", "given": "Paul A", "initials": "PA"}, {"family": "Franke", "given": "Barbara", "initials": "B", "orcid": "0000-0003-4375-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/105f0131cfc34a668ed840e622e4f902.json"}}, {"family": "Bennett", "given": "David A", "initials": "DA"}, {"family": "Grabe", "given": "Hans J", "initials": "HJ", "orcid": "0000-0003-3684-4208", "researcher": {"href": "https://publications.scilifelab.se/researcher/d660f9169e6c4c8485041382ebf71e3d.json"}}, {"family": "Johnson", "given": "Andrew D", "initials": "AD"}, {"family": "Chen", "given": "Christopher", "initials": "C"}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "Lopez", "given": "Oscar L", "initials": "OL"}, {"family": "Fornage", "given": "Myriam", "initials": "M"}, {"family": "Wardlaw", "given": "Joanna M", "initials": "JM", "orcid": "0000-0002-9812-6642", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fd13301b0e34ae88b49d5d40145bb74.json"}}, {"family": "Schmidt", "given": "Reinhold", "initials": "R"}, {"family": "DeCarli", "given": "Charles", "initials": "C"}, {"family": "De Jager", "given": "Philip L", "initials": "PL", "orcid": "0000-0002-8057-2505", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fb514edc45a46b688ef0fa75250a322.json"}}, {"family": "Villringer", "given": "Arno", "initials": "A"}, {"family": "Debette", "given": "St\u00e9phanie", "initials": "S"}, {"family": "Gudnason", "given": "Vilmundur", "initials": "V", "orcid": "0000-0001-5696-0084", "researcher": {"href": "https://publications.scilifelab.se/researcher/d18327939c1541acba054b2340ac174f.json"}}, {"family": "Medland", "given": "Sarah E", "initials": "SE", "orcid": "0000-0003-1382-380X", "researcher": {"href": "https://publications.scilifelab.se/researcher/da1f0230a912425c9237830be85aa642.json"}}, {"family": "Shulman", "given": "Joshua M", "initials": "JM"}, {"family": "Thompson", "given": "Paul M", "initials": "PM"}, {"family": "Seshadri", "given": "Sudha", "initials": "S"}, {"family": "Ikram", "given": "M Arfan", "initials": "MA", "orcid": "0000-0003-0372-8585", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ec81571f4a94af682b4e23526f87385.json"}}], "type": "journal article", "published": "2019-11-00", "journal": {"volume": "51", "issn": "1546-1718", "issue": "11", "pages": "1624-1636", "title": "Nat. Genet.", "issn-l": "1061-4036"}, "abstract": "Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.", "doi": "10.1038/s41588-019-0511-y", "pmid": "31636452", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41588-019-0511-y"}, {"db": "pmc", "key": "PMC7055269"}, {"db": "mid", "key": "NIHMS1553652"}], "notes": [], "created": "2019-10-22T06:26:22.885Z", "modified": "2021-06-18T13:55:45.367Z"}]}