Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels

Chloé Sarnowski*, Mohsen Ghanbari, Joshua C. Bis, Mark Logue, Myriam Fornage, Aniket Mishra, Shahzad Ahmad, Alexa S. Beiser, Eric Boerwinkle, Vincent Bouteloup, Vincent Chouraki, L. Adrienne Cupples, Vincent Damotte, Charles S. DeCarli, Anita L. DeStefano, Luc Djoussé, Alison E. Fohner, Carol E. Franz, Tiffany F. Kautz, Jean Charles LambertMichael J. Lyons, Thomas H. Mosley, Kenneth J. Mukamal, Matthew P. Pase, Eliana C. Portilla Fernandez, Robert A. Rissman, Claudia L. Satizabal, Ramachandran S. Vasan, Amber Yaqub, Stephanie Debette, Carole Dufouil, Lenore J. Launer, William S. Kremen, William T. Longstreth, M. Arfan Ikram, Sudha Seshadri

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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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 × 10−8. We additionally detected 14 novel loci at P < 5 × 10−7, 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.

Original languageEnglish
Article number336
JournalCommunications Biology
Issue number1
Publication statusPublished - 8 Apr 2022

Bibliographical note

Funding Information:
We thank all the participating cohorts from the CHARGE consortium and ADNI participants for contributing to this study. Detailed study-specific acknowledgements are provided in the Supplementary Notes 11 and 12.

Publisher Copyright:
© 2022, The Author(s).


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