Faculty, Staff and Student Publications
Publication Date
4-8-2022
Journal
Communications Biology
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.
Keywords
Black or African American, Alzheimer Disease, Exome, Genome-Wide Association Study, Humans, Tauopathies, Genome-wide association studies, Genetic variation
DOI
10.1038/s42003-022-03287-y
PMID
35396452
PMCID
PMC8993877
PubMedCentral® Posted Date
4-8-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Medical Genetics Commons, Public Health Commons
