| Title | Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Sarnowski C, Ghanbari M, Bis JC, Logue M, Fornage M, Mishra A, Ahmad S, Beiser AS, Boerwinkle E, Bouteloup V, Chouraki V, L Cupples A, Damotte V, DeCarli CS, DeStefano AL, Djoussé L, Fohner AE, Franz CE, Kautz TF, Lambert J-C, Lyons MJ, Mosley TH, Mukamal KJ, Pase MP, Fernandez ECPortilla, Rissman RA, Satizabal CL, Vasan RS, Yaqub A, Debette S, Dufouil C, Launer LJ, Kremen WS, Longstreth WT, M Ikram A, Seshadri S |
| Journal | Commun Biol |
| Volume | 5 |
| Issue | 1 |
| Pagination | 336 |
| Date Published | 2022 04 08 |
| ISSN | 2399-3642 |
| Keywords | African Americans, Alzheimer Disease, Exome, Genome-Wide Association Study, Humans, Tauopathies |
| 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. We additionally detected 14 novel loci at P < 5 × 10, 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. |
| DOI | 10.1038/s42003-022-03287-y |
| Alternate Journal | Commun Biol |
| PubMed ID | 35396452 |
| PubMed Central ID | PMC8993877 |
| Grant List | R01 NS017950 / NS / NINDS NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States K99 AG066849 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 AG058589 / AG / NIA NIH HHS / United States |