{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sarnowski C"],"funding":["U.S. Department of Health &amp; Human Services | NIH | National Institute of Neurological Disorders and Stroke","NIA NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging","NHLBI NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute","NINDS NIH HHS"],"pagination":["336"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8993877"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(1)"],"pubmed_abstract":["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 MAPT 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 P < 5 × 10<sup>-8</sup>. We additionally detected 14 novel loci at P < 5 × 10<sup>-7</sup>, 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's, and Parkinson's (F5, MAP1B, and BCAS3), with Alzheimer's pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry."],"journal":["Communications biology"],"pubmed_title":["Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels."],"pmcid":["PMC8993877"],"funding_grant_id":["K99AG066849","AG052409","RF1 AG059421","U01 HL096917","R01 AG064955","U01 AG058589","AG058589","HL093029","R01 AG022381","R01 AG054076","HL096917","AG049607","P30 AG066546","K99 AG066849","R01 NS017950","U01 AG052409","R01 AG050595","AG049505","AG059421","K01 AG071689","P30 AG066530","AG054076","NS017950","NS100605","R01 HL105756"],"pubmed_authors":["Cupples LA","Logue M","Franz CE","Mukamal KJ","Ahmad S","Yaqub A","Boerwinkle E","Djousse L","Kremen WS","Satizabal CL","Mosley TH","Rissman RA","Ikram MA","Kautz TF","Chouraki V","Dufouil C","Ghanbari M","Vasan RS","Portilla Fernandez EC","Debette S","Lyons MJ","Lambert JC","Longstreth WT","Seshadri S","Bis JC","Fohner AE","Beiser AS","Mishra A","Damotte V","DeCarli CS","Launer LJ","DeStefano AL","Pase MP","Fornage M","Sarnowski C","Bouteloup V"],"additional_accession":[]},"is_claimable":false,"name":"Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.","description":"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 MAPT 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 P < 5 × 10<sup>-8</sup>. We additionally detected 14 novel loci at P < 5 × 10<sup>-7</sup>, 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's, and Parkinson's (F5, MAP1B, and BCAS3), with Alzheimer's pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-10T01:34:33.397Z","creation":"2025-04-20T03:08:22.759Z"},"accession":"S-EPMC8993877","cross_references":{"pubmed":["35396452"],"doi":["10.1038/s42003-022-03287-y"]}}