학술논문
Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.
Document Type
Article
Author
Sarnowski, Chloé; 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.; Djoussé, Luc; Fohner, Alison E.; Franz, Carol E.; Kautz, Tiffany F.; Lambert, Jean-Charles
Source
Subject
*GENOME-wide association studies
*ALZHEIMER'S disease
*PARKINSON'S disease
*ETIOLOGY of diseases
*NEUROLOGICAL disorders
*PHENOTYPES
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Language
ISSN
2399-3642
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 × 10−8. 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. A meta-analysis of genome-wide association studies of circulating total-tau levels identifies loci specific to European or African American ancestries, providing further insight to the genetic etiology of neurological diseases. [ABSTRACT FROM AUTHOR]