{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:33:41Z","timestamp":1792791221735,"version":"4.5.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["K99AG066849"],"award-info":[{"award-number":["K99AG066849"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG054076"],"award-info":[{"award-number":["AG054076"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG049607"],"award-info":[{"award-number":["AG049607"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG059421"],"award-info":[{"award-number":["AG059421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG049505"],"award-info":[{"award-number":["AG049505"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG052409"],"award-info":[{"award-number":["AG052409"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG058589"],"award-info":[{"award-number":["AG058589"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS017950"],"award-info":[{"award-number":["NS017950"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["NS100605"],"award-info":[{"award-number":["NS100605"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL093029"],"award-info":[{"award-number":["HL093029"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL096917"],"award-info":[{"award-number":["HL096917"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21\n                    <jats:italic>MAPT<\/jats:italic>\n                    locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    . We additionally detected 14 novel loci at\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22127<\/jats:sup>\n                    , specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer\u2019s, and Parkinson\u2019s (\n                    <jats:italic>F<\/jats:italic>\n                    5,\n                    <jats:italic>MAP1B<\/jats:italic>\n                    , and\n                    <jats:italic>BCAS3<\/jats:italic>\n                    ), with Alzheimer\u2019s pathological hallmarks (\n                    <jats:italic>ADAMTS12<\/jats:italic>\n                    ,\n                    <jats:italic>IL15<\/jats:italic>\n                    , and\n                    <jats:italic>FHIT<\/jats:italic>\n                    ), or with an important function in the brain (\n                    <jats:italic>PARD3<\/jats:italic>\n                    ,\n                    <jats:italic>ELFN2<\/jats:italic>\n                    ,\n                    <jats:italic>UBASH3B<\/jats:italic>\n                    ,\n                    <jats:italic>SLIT3<\/jats:italic>\n                    , and\n                    <jats:italic>NSD3<\/jats:italic>\n                    ), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.\n                  <\/jats:p>","DOI":"10.1038\/s42003-022-03287-y","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T06:11:21Z","timestamp":1649398281000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6090-7099","authenticated-orcid":false,"given":"Chlo\u00e9","family":"Sarnowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9476-7143","authenticated-orcid":false,"given":"Mohsen","family":"Ghanbari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3409-1110","authenticated-orcid":false,"given":"Joshua C.","family":"Bis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Logue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0677-8158","authenticated-orcid":false,"given":"Myriam","family":"Fornage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8141-1543","authenticated-orcid":false,"given":"Aniket","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-3790","authenticated-orcid":false,"given":"Shahzad","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa S.","family":"Beiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bouteloup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Chouraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-7965","authenticated-orcid":false,"given":"L Adrienne","family":"Cupples","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Damotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"DeCarli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita L.","family":"DeStefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Djouss\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison E.","family":"Fohner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-1755","authenticated-orcid":false,"given":"Carol E.","family":"Franz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany F.","family":"Kautz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-7817","authenticated-orcid":false,"given":"Jean-Charles","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Lyons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Mosley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8450-6970","authenticated-orcid":false,"given":"Kenneth J.","family":"Mukamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4143-8485","authenticated-orcid":false,"given":"Matthew P.","family":"Pase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana C.","family":"Portilla Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Rissman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L.","family":"Satizabal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-5970","authenticated-orcid":false,"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3579-8054","authenticated-orcid":false,"given":"Amber","family":"Yaqub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-7968","authenticated-orcid":false,"given":"Stephanie","family":"Debette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2442-4476","authenticated-orcid":false,"given":"Carole","family":"Dufouil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3238-7612","authenticated-orcid":false,"given":"Lenore J.","family":"Launer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8629-5609","authenticated-orcid":false,"given":"William S.","family":"Kremen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Longstreth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0372-8585","authenticated-orcid":false,"given":"M Arfan","family":"Ikram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"3287_CR1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2217\/17520363.2.4.363","volume":"2","author":"S Schraen-Maschke","year":"2008","unstructured":"Schraen-Maschke, S. et al. Tau as a biomarker of neurodegenerative diseases. Biomark. Med. 2, 363\u2013384 (2008).","journal-title":"Biomark. Med."},{"key":"3287_CR2","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/S1474-4422(03)00530-1","volume":"2","author":"K Blennow","year":"2003","unstructured":"Blennow, K. & Hampel, H. CSF markers for incipient Alzheimer\u2019s disease. Lancet Neurol. 2, 605\u2013613 (2003).","journal-title":"Lancet Neurol."},{"key":"3287_CR3","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S1474-4422(16)00070-3","volume":"15","author":"B Olsson","year":"2016","unstructured":"Olsson, B. et al. CSF and blood biomarkers for the diagnosis of Alzheimer\u2019s disease: a systematic review and meta-analysis. Lancet Neurol. 15, 673\u2013684 (2016).","journal-title":"Lancet Neurol."},{"key":"3287_CR4","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1212\/WNL.0000000000002081","volume":"86","author":"MD Zwan","year":"2016","unstructured":"Zwan, M. D. et al. Use of amyloid-PET to determine cutpoints for CSF markers: a multicenter study. Neurology 86, 50\u201358 (2016).","journal-title":"Neurology"},{"key":"3287_CR5","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1136\/jnnp-2014-308004","volume":"86","author":"D Wagshal","year":"2015","unstructured":"Wagshal, D. et al. Divergent CSF tau alterations in two common tauopathies: Alzheimer\u2019s disease and progressive supranuclear palsy. J. Neurol. Neurosurg. Psychiatry 86, 244\u2013250 (2015).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"3287_CR6","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1001\/archneur.60.9.1209","volume":"60","author":"SM Rosso","year":"2003","unstructured":"Rosso, S. M. et al. Total tau and phosphorylated tau 181 levels in the cerebrospinal fluid of patients with frontotemporal dementia due to P301L and G272V tau mutations. Arch. Neurol. 60, 1209\u20131213 (2003).","journal-title":"Arch. Neurol."},{"key":"3287_CR7","doi-asserted-by":"crossref","unstructured":"Zetterberg, H. & Burnham, S. C. Blood-based molecular biomarkers for Alzheimer\u2019s disease. Mol. Brain 12, 26-019-0448-1 (2019).","DOI":"10.1186\/s13041-019-0448-1"},{"key":"3287_CR8","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","volume":"25","author":"DA Nation","year":"2019","unstructured":"Nation, D. A. et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat. Med. 25, 270\u2013276 (2019).","journal-title":"Nat. Med."},{"key":"3287_CR9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.2174\/187152709787601867","volume":"8","author":"R Deane","year":"2009","unstructured":"Deane, R., Bell, R. D., Sagare, A. & Zlokovic, B. V. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer\u2019s disease. CNS Neurol. Disord. Drug Targets 8, 16\u201330 (2009).","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"3287_CR10","doi-asserted-by":"crossref","unstructured":"Pase, M. P. et al. Assessment of Plasma Total Tau Level as a predictive biomarker for dementia and related endophenotypes. JAMA Neurol. 76, 598\u2013606 (2019).","DOI":"10.1001\/jamaneurol.2018.4666"},{"key":"3287_CR11","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.jalz.2016.06.001","volume":"12","author":"JL Dage","year":"2016","unstructured":"Dage, J. L. et al. Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort. Alzheimers Dement 12, 1226\u20131234 (2016).","journal-title":"Alzheimers Dement"},{"key":"3287_CR12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/alzrt163","volume":"5","author":"H Zetterberg","year":"2013","unstructured":"Zetterberg, H. et al. Plasma tau levels in Alzheimer\u2019s disease. Alzheimers Res. Ther. 5, 9 (2013).","journal-title":"Alzheimers Res. Ther."},{"key":"3287_CR13","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1212\/WNL.0000000000003246","volume":"87","author":"N Mattsson","year":"2016","unstructured":"Mattsson, N. et al. Plasma tau in Alzheimer disease. Neurology 87, 1827\u20131835 (2016).","journal-title":"Neurology"},{"key":"3287_CR14","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1001\/jamaneurol.2017.1359","volume":"74","author":"MM Mielke","year":"2017","unstructured":"Mielke, M. M. et al. Association of Plasma Total Tau Level with cognitive decline and risk of mild cognitive impairment or dementia in the mayo clinic study on aging. JAMA Neurol. 74, 1073\u20131080 (2017).","journal-title":"JAMA Neurol."},{"key":"3287_CR15","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1002\/ana.25542","volume":"86","author":"MP Pase","year":"2019","unstructured":"Pase, M. P. et al. Plasma total-tau as a biomarker of stroke risk in the community. Ann. Neurol. 86, 463\u2013467 (2019).","journal-title":"Ann. Neurol."},{"key":"3287_CR16","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.dadm.2019.05.001","volume":"11","author":"S Fossati","year":"2019","unstructured":"Fossati, S. et al. Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer\u2019s disease. Alzheimers Dement. (Amst.) 11, 483\u2013492 (2019).","journal-title":"Alzheimers Dement. (Amst.)"},{"key":"3287_CR17","doi-asserted-by":"publisher","unstructured":"Nam, E., Lee, Y. B., Moon, C. & Chang, K. A. Serum Tau proteins as potential biomarkers for the assessment of Alzheimer\u2019s disease progression. Int. J. Mol. Sci. 21, https:\/\/doi.org\/10.3390\/ijms21145007 (2020).","DOI":"10.3390\/ijms21145007"},{"key":"3287_CR18","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1212\/WNL.0000000000003615","volume":"88","author":"J Chen","year":"2017","unstructured":"Chen, J. et al. Genome-wide association study identifies MAPT locus influencing human plasma tau levels. Neurology 88, 669\u2013676 (2017).","journal-title":"Neurology"},{"key":"3287_CR19","doi-asserted-by":"crossref","unstructured":"Lord, J. et al. A genome-wide association study of plasma phosphorylated tau181. Neurobiol. Aging 106, 304.e1\u2013304.e3 (2021).","DOI":"10.1016\/j.neurobiolaging.2021.04.018"},{"key":"3287_CR20","doi-asserted-by":"publisher","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","volume":"45","author":"J MacArthur","year":"2017","unstructured":"MacArthur, J. et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 45, D896\u2013D901 (2017).","journal-title":"Nucleic Acids Res."},{"key":"3287_CR21","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/ng.859","volume":"43","author":"GU Hoglinger","year":"2011","unstructured":"Hoglinger, G. U. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699\u2013705 (2011).","journal-title":"Nat. Genet."},{"key":"3287_CR22","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/mp.2015.23","volume":"21","author":"G Jun","year":"2016","unstructured":"Jun, G. et al. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol. Psychiatry 21, 108\u2013117 (2016).","journal-title":"Mol. Psychiatry"},{"key":"3287_CR23","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1038\/nn.4398","volume":"19","author":"HH Adams","year":"2016","unstructured":"Adams, H. H. et al. Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat. Neurosci. 19, 1569\u20131582 (2016).","journal-title":"Nat. Neurosci."},{"key":"3287_CR24","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/nature14101","volume":"520","author":"DP Hibar","year":"2015","unstructured":"Hibar, D. P. et al. Common genetic variants influence human subcortical brain structures. Nature 520, 224\u2013229 (2015).","journal-title":"Nature"},{"key":"3287_CR25","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1093\/cercor\/bhaa035","volume":"30","author":"J Shin","year":"2020","unstructured":"Shin, J. et al. Global and regional development of the human cerebral cortex: molecular architecture and occupational aptitudes. Cereb. Cortex 30, 4121\u20134139 (2020).","journal-title":"Cereb. Cortex"},{"key":"3287_CR26","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3389\/fneur.2018.00809","volume":"9","author":"X Zhang","year":"2018","unstructured":"Zhang, X. et al. Tau pathology in Parkinson\u2019s disease. Front. Neurol. 9, 809 (2018).","journal-title":"Front. Neurol."},{"key":"3287_CR27","doi-asserted-by":"crossref","unstructured":"Meddens, S. F. W. et al. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle. Mol. Psychiatry 26, 2056\u20132069 (2021).","DOI":"10.1038\/s41380-020-0697-5"},{"key":"3287_CR28","doi-asserted-by":"crossref","unstructured":"Doherty, A. et al. GWAS identifies 14 loci for device-measured physical activity and sleep duration. Nat. Commun. 9, 5257 (2018).","DOI":"10.1038\/s41467-018-07743-4"},{"key":"3287_CR29","doi-asserted-by":"publisher","first-page":"e46199","DOI":"10.1371\/journal.pone.0046199","volume":"7","author":"JC Latourelle","year":"2012","unstructured":"Latourelle, J. C., Dumitriu, A., Hadzi, T. C., Beach, T. G. & Myers, R. H. Evaluation of Parkinson disease risk variants as expression-QTLs. PLoS ONE 7, e46199 (2012).","journal-title":"PLoS ONE"},{"key":"3287_CR30","doi-asserted-by":"publisher","first-page":"e0117282","DOI":"10.1371\/journal.pone.0117282","volume":"10","author":"RJ Bishnoi","year":"2015","unstructured":"Bishnoi, R. J., Palmer, R. F. & Royall, D. R. Serum interleukin (IL)-15 as a biomarker of Alzheimer\u2019s disease. PLoS ONE 10, e0117282 (2015).","journal-title":"PLoS ONE"},{"key":"3287_CR31","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.33594\/000000069","volume":"52","author":"T Fontanil","year":"2019","unstructured":"Fontanil, T. et al. Neurocan is a new substrate for the ADAMTS12 metalloprotease: potential implications in neuropathies. Cell. Physiol. Biochem. 52, 1003\u20131016 (2019).","journal-title":"Cell. Physiol. Biochem."},{"key":"3287_CR32","doi-asserted-by":"publisher","first-page":"5231","DOI":"10.1182\/blood-2012-07-442038","volume":"120","author":"A Arning","year":"2012","unstructured":"Arning, A. et al. A genome-wide association study identifies a gene network of ADAMTS genes in the predisposition to pediatric stroke. Blood 120, 5231\u20135236 (2012).","journal-title":"Blood"},{"key":"3287_CR33","doi-asserted-by":"publisher","first-page":"e0237928","DOI":"10.1371\/journal.pone.0237928","volume":"15","author":"A Witten","year":"2020","unstructured":"Witten, A. et al. ADAMTS12, a new candidate gene for pediatric stroke. PLoS ONE 15, e0237928 (2020).","journal-title":"PLoS ONE"},{"key":"3287_CR34","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/j.neuint.2007.10.020","volume":"52","author":"G Gevorkian","year":"2008","unstructured":"Gevorkian, G. et al. Amyloid-beta peptide binds to microtubule-associated protein 1B (MAP1B). Neurochem. Int. 52, 1030\u20131036 (2008).","journal-title":"Neurochem. Int."},{"key":"3287_CR35","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/0896-6273(90)90144-5","volume":"4","author":"M Hasegawa","year":"1990","unstructured":"Hasegawa, M., Arai, T. & Ihara, Y. Immunochemical evidence that fragments of phosphorylated MAP5 (MAP1B) are bound to neurofibrillary tangles in Alzheimer\u2019s disease. Neuron 4, 909\u2013918 (1990).","journal-title":"Neuron"},{"key":"3287_CR36","doi-asserted-by":"publisher","first-page":"21500","DOI":"10.1074\/jbc.M000099200","volume":"275","author":"PH Jensen","year":"2000","unstructured":"Jensen, P. H. et al. Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments. J. Biol. Chem. 275, 21500\u201321507 (2000).","journal-title":"J. Biol. Chem."},{"key":"3287_CR37","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1091\/mbc.E18-08-0484","volume":"30","author":"D Joshi","year":"2019","unstructured":"Joshi, D. & Inamdar, M. S. Rudhira\/BCAS3 couples microtubules and intermediate filaments to promote cell migration for angiogenic remodeling. Mol. Biol. Cell 30, 1437\u20131450 (2019).","journal-title":"Mol. Biol. Cell"},{"key":"3287_CR38","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1161\/STROKEAHA.115.011328","volume":"47","author":"YC Cheng","year":"2016","unstructured":"Cheng, Y. C. et al. Genome-Wide Association analysis of young-onset stroke identifies a locus on chromosome 10q25 Near HABP2. Stroke 47, 307\u2013316 (2016).","journal-title":"Stroke"},{"key":"3287_CR39","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","volume":"558","author":"BB Sun","year":"2018","unstructured":"Sun, B. B. et al. Genomic atlas of the human plasma proteome. Nature 558, 73\u201379 (2018).","journal-title":"Nature"},{"key":"3287_CR40","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1093\/hmg\/ddw037","volume":"25","author":"DA Hinds","year":"2016","unstructured":"Hinds, D. A. et al. Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis. Hum. Mol. Genet. 25, 1867\u20131874 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"3287_CR41","doi-asserted-by":"publisher","first-page":"592","DOI":"10.3389\/fnins.2018.00592","volume":"12","author":"MW Logue","year":"2018","unstructured":"Logue, M. W. et al. Targeted Sequencing of Alzheimer disease genes in African Americans implicates novel risk variants. Front. Neurosci. 12, 592 (2018).","journal-title":"Front. Neurosci."},{"key":"3287_CR42","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1002\/ana.23644","volume":"72","author":"SA Melville","year":"2012","unstructured":"Melville, S. A. et al. Multiple loci influencing hippocampal degeneration identified by genome scan. Ann. Neurol. 72, 65\u201375 (2012).","journal-title":"Ann. Neurol."},{"key":"3287_CR43","doi-asserted-by":"publisher","first-page":"33571","DOI":"10.1074\/jbc.M109.055897","volume":"284","author":"MR Khazaei","year":"2009","unstructured":"Khazaei, M. R. & Puschel, A. W. Phosphorylation of the par polarity complex protein Par3 at serine 962 is mediated by aurora a and regulates its function in neuronal polarity. J. Biol. Chem. 284, 33571\u201333579 (2009).","journal-title":"J. Biol. Chem."},{"key":"3287_CR44","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/humu.23153","volume":"38","author":"X Chen","year":"2017","unstructured":"Chen, X. et al. Rare Deleterious PARD3 Variants in the aPKC-Binding Region are implicated in the pathogenesis of human cranial neural tube defects via disrupting apical tight junction formation. Hum. Mutat. 38, 378\u2013389 (2017).","journal-title":"Hum. Mutat."},{"key":"3287_CR45","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.devcel.2012.11.014","volume":"24","author":"S Chen","year":"2013","unstructured":"Chen, S. et al. Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity. Dev. Cell. 24, 26\u201340 (2013).","journal-title":"Dev. Cell."},{"key":"3287_CR46","doi-asserted-by":"publisher","first-page":"8534","DOI":"10.1073\/pnas.0509955103","volume":"103","author":"YM Chen","year":"2006","unstructured":"Chen, Y. M. et al. Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3\/PAR-6\/atypical PKC complex in regulating hippocampal neuronal polarity. Proc. Natl Acad. Sci. U. S. A. 103, 8534\u20138539 (2006).","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"3287_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2016.03.022","volume":"93","author":"M Sun","year":"2016","unstructured":"Sun, M., Asghar, S. Z. & Zhang, H. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb. Neurobiol. Dis. 93, 1\u201311 (2016).","journal-title":"Neurobiol. Dis."},{"key":"3287_CR48","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neurobiolaging.2019.01.023","volume":"77","author":"M Sun","year":"2019","unstructured":"Sun, M., Huang, C., Wang, H. & Zhang, H. Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons. Neurobiol. Aging 77, 87\u201393 (2019).","journal-title":"Neurobiol. Aging"},{"key":"3287_CR49","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.neurobiolaging.2017.08.024","volume":"60","author":"M Sun","year":"2017","unstructured":"Sun, M. & Zhang, H. Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1. Neurobiol. Aging 60, 129\u2013140 (2017).","journal-title":"Neurobiol. Aging"},{"key":"3287_CR50","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1038\/s41380-019-0512-3","volume":"24","author":"HA Dunn","year":"2019","unstructured":"Dunn, H. A., Zucca, S., Dao, M., Orlandi, C. & Martemyanov, K. A. ELFN2 is a postsynaptic cell adhesion molecule with essential roles in controlling group III mGluRs in the brain and neuropsychiatric behavior. Mol. Psychiatry 24, 1902\u20131919 (2019).","journal-title":"Mol. Psychiatry"},{"key":"3287_CR51","doi-asserted-by":"publisher","first-page":"634875","DOI":"10.3389\/fncir.2021.634875","volume":"15","author":"H Matsunaga","year":"2021","unstructured":"Matsunaga, H. & Aruga, J. Trans-Synaptic regulation of metabotropic glutamate receptors by Elfn proteins in health and disease. Front. Neural Circuits 15, 634875 (2021).","journal-title":"Front. Neural Circuits"},{"key":"3287_CR52","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.bbr.2015.12.033","volume":"303","author":"R Smidak","year":"2016","unstructured":"Smidak, R. et al. Quantitative proteomics reveals protein kinases and phosphatases in the individual phases of contextual fear conditioning in the C57BL\/6J mouse. Behav. Brain Res. 303, 208\u2013217 (2016).","journal-title":"Behav. Brain Res."},{"key":"3287_CR53","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/dvg.22852","volume":"53","author":"B Punnamoottil","year":"2015","unstructured":"Punnamoottil, B., Rinkwitz, S., Giacomotto, J., Svahn, A. J. & Becker, T. S. Motor neuron-expressed microRNAs 218 and their enhancers are nested within introns of Slit2\/3 genes. Genesis 53, 321\u2013328 (2015).","journal-title":"Genesis"},{"key":"3287_CR54","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S0092-8674(00)80590-5","volume":"96","author":"K Brose","year":"1999","unstructured":"Brose, K. et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96, 795\u2013806 (1999).","journal-title":"Cell"},{"key":"3287_CR55","doi-asserted-by":"publisher","first-page":"e0220512","DOI":"10.1371\/journal.pone.0220512","volume":"14","author":"Z Odgerel","year":"2019","unstructured":"Odgerel, Z. et al. Whole genome sequencing and rare variant analysis in essential tremor families. PLoS ONE 14, e0220512 (2019).","journal-title":"PLoS ONE"},{"key":"3287_CR56","doi-asserted-by":"crossref","unstructured":"Das, A. et al. Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia. J. Neuroinflammation 13, 182 (2016).","DOI":"10.1186\/s12974-016-0644-1"},{"key":"3287_CR57","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3233\/JAD-200828","volume":"79","author":"K Deniz","year":"2021","unstructured":"Deniz, K. et al. Plasma Biomarkers of Alzheimer\u2019s Disease in African Americans. J. Alzheimers Dis. 79, 323\u2013334 (2021).","journal-title":"J. Alzheimers Dis."},{"key":"3287_CR58","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190\u20132191 (2010).","journal-title":"Bioinformatics"},{"key":"3287_CR59","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.ajhg.2011.04.014","volume":"88","author":"B Han","year":"2011","unstructured":"Han, B. & Eskin, E. Random-effects model aimed at discovering associations in meta-analysis of genome-wide association studies. Am. J. Hum. Genet. 88, 586\u2013598 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"3287_CR60","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1534\/g3.116.029439","volume":"6","author":"EY Kang","year":"2016","unstructured":"Kang, E. Y. et al. ForestPMPlot: a flexible tool for visualizing heterogeneity between studies in meta-analysis. G3 (Bethesda) 6, 1793\u20131798 (2016).","journal-title":"G3 (Bethesda)"},{"key":"3287_CR61","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","volume":"88","author":"J Yang","year":"2011","unstructured":"Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76\u201382 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"3287_CR62","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/ng.2213","volume":"44","author":"J Yang","year":"2012","unstructured":"Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369\u2013375 (2012).","journal-title":"Nat. Genet."},{"key":"3287_CR63","doi-asserted-by":"crossref","unstructured":"Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8, 1826 (2017).","DOI":"10.1038\/s41467-017-01261-5"},{"key":"3287_CR64","doi-asserted-by":"crossref","unstructured":"Watanabe, K., Umicevic Mirkov, M., de Leeuw, C. A., van den Heuvel, M. P. & Posthuma, D. Genetic mapping of cell type specificity for complex traits. Nat. Commun. 10, 3222 (2019).","DOI":"10.1038\/s41467-019-11181-1"},{"key":"3287_CR65","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41588-018-0058-3","volume":"50","author":"R Malik","year":"2018","unstructured":"Malik, R. et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat. Genet. 50, 524\u2013537 (2018).","journal-title":"Nat. Genet."},{"key":"3287_CR66","first-page":"93","volume":"375","author":"C Satizabal","year":"2016","unstructured":"Satizabal, C., Beiser, A. S. & Seshadri, S. Incidence of dementia over three decades in the Framingham Heart Study. N. Engl. J. Med. 375, 93\u201394 (2016).","journal-title":"N. Engl. J. Med."},{"key":"3287_CR67","doi-asserted-by":"publisher","first-page":"e188","DOI":"10.1212\/WNL.0000000000004820","volume":"90","author":"C Sarnowski","year":"2018","unstructured":"Sarnowski, C. et al. Whole genome sequence analyses of brain imaging measures in the Framingham Study. Neurology 90, e188\u2013e196 (2018).","journal-title":"Neurology"},{"key":"3287_CR68","doi-asserted-by":"publisher","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","volume":"13","author":"G Hemani","year":"2017","unstructured":"Hemani, G., Tilling, K. & Davey Smith, G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet. 13, e1007081 (2017).","journal-title":"PLoS Genet."},{"key":"3287_CR69","doi-asserted-by":"publisher","unstructured":"Hemani, G. et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife 7, https:\/\/doi.org\/10.7554\/eLife.34408 (2018).","DOI":"10.7554\/eLife.34408"},{"key":"3287_CR70","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1161\/CIRCGENETICS.108.829747","volume":"2","author":"BM Psaty","year":"2009","unstructured":"Psaty, B. M. et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ. Cardiovasc. Genet. 2, 73\u201380 (2009).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"3287_CR71","doi-asserted-by":"publisher","first-page":"e68095","DOI":"10.1371\/journal.pone.0068095","volume":"8","author":"ML Grove","year":"2013","unstructured":"Grove, M. L. et al. Best practices and joint calling of the HumanExome BeadChip: the CHARGE Consortium. PLoS ONE 8, e68095 (2013).","journal-title":"PLoS ONE"},{"key":"3287_CR72","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1002\/humu.21517","volume":"32","author":"X Liu","year":"2011","unstructured":"Liu, X., Jian, X. & Boerwinkle, E. dbNSFP: a lightweight database of human nonsynonymous SNPs and their functional predictions. Hum. Mutat. 32, 894\u2013899 (2011).","journal-title":"Hum. Mutat."},{"key":"3287_CR73","doi-asserted-by":"crossref","unstructured":"McLaren, W. et al. The ensembl variant effect predictor. Genome Biol. 17, 122 (2016).","DOI":"10.1186\/s13059-016-0974-4"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03287-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03287-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03287-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T03:33:51Z","timestamp":1669347231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03287-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3287"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03287-y","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,8]]},"assertion":[{"value":"3 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.S.D. reports personal fees from Novartis Pharmaceutical outside the submitted work. All the other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"336"}}