SARNOWSKI, Chloe; GHANBARI, Mohsen; BIS, Joshua C.; LOGUE, Mark; FORNAGE, Myriam; MISHRA, Aniket; AHMAD, Shahzad; BEISER, Alexa S.; BOERWINKLE, Eric; BOUTELOUP, Vincent; CHOURAKI, Vincent; CUPPLES, L. Adrienne; DAMOTTE, Vincent; DECARLI, Charles S.; DESTEFANO, Anita L.; DJOUSSE, Luc; FOHNER, Alison E.; FRANZ, Carol E.; KAUTZ, Tiffany F.; LAMBERT, Jean-Charles; LYONS, Michael J.; MOSLEY, Thomas H.; MUKAMAL, Kenneth J.; PASE, Matthew P.; PORTILLA FERNANDEZ, Eliana C.; RISSMAN, Robert A.; SATIZABAL, Claudia L.; VASAN, Ramachandran S.; YAQUB, Amber; DEBETTE, Stephanie; DUFOUIL, Carole; LAUNER, Lenore J.; KREMEN, William S.; LONGSTRETH, William T.; IKRAM, M. Arfan; SESHADRI, Sudha

doi:10.1038/s42003-022-03287-y

Langue

Article de revue

Ce document a été publié dans

Communications Biology. 2022-04-08, vol. 5, n° 1

Résumé en anglais

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.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/140035

DOI

http://dx.doi.org/10.1038/s42003-022-03287-y

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

Voir/Ouvrir

Métadonnées

Partager cette publication !

Licence d’utilisation du document

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

Langue

Ce document a été publié dans

Résumé en anglais

URI

DOI

Unités de recherche