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

被引：12

作者：

Sarnowski, Chloe ^{[1
]}

Ghanbari, Mohsen ^{[2
,3
]}

Bis, Joshua C. ^{[4
]}

Logue, Mark ^{[5
,6
]}

Fornage, Myriam ^{[7
]}

Mishra, Aniket ^{[8
]}

Ahmad, Shahzad ^{[2
,9
]}

Beiser, Alexa S. ^{[10
,11
,12
,13
]}

Boerwinkle, Eric ^{[7
]}

Bouteloup, Vincent ^{[14
]}

Chouraki, Vincent ^{[15
]}

Cupples, L. Adrienne ^{[10
,11
,12
]}

Damotte, Vincent ^{[15
]}

DeCarli, Charles S. ^{[16
,17
]}

DeStefano, Anita L. ^{[10
]}

Djousse, Luc ^{[18
,19
]}

Fohner, Alison E. ^{[20
,21
,22
]}

Franz, Carol E. ^{[23
,24
]}

Kautz, Tiffany F. ^{[25
]}

Lambert, Jean-Charles ^{[15
]}

Lyons, Michael J. ^{[26
]}

Mosley, Thomas H. ^{[27
]}

Mukamal, Kenneth J. ^{[28
]}

Pase, Matthew P. ^{[29
,30
]}

Fernandez, Eliana C. Portilla ^{[2
]}

Rissman, Robert A. ^{[31
]}

Satizabal, Claudia L. ^{[11
,12
,13
,25
]}

Vasan, Ramachandran S. ^{[11
,12
,32
]}

Yaqub, Amber ^{[2
]}

Debette, Stephanie ^{[8
,33
]}

Dufouil, Carole ^{[33
]}

Launer, Lenore J. ^{[34
]}

Kremen, William S. ^{[23
,24
]}

Longstreth, William T. ^{[21
,35
]}

Ikram, M. Arfan ^{[2
]}

Seshadri, Sudha ^{[11
,12
,13
,25
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA

[2] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[3] Mashhad Univ Med Sci, Sch Med, Dept Genet, Mashhad, Razavi Khorasan, Iran

[4] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[5] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA

[6] Boston Univ, Sch Med, Dept Psychiat & Biomed Genet, Boston, MA 02118 USA

[7] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA

[8] Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, Team VINTAGE,UMR 1219, F-33000 Bordeaux, France

[9] Leiden Univ, Leiden Acad Ctr Drug Res, Div Syst Biomed & Pharmacol, Leiden, Netherlands

[10] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[11] Boston Univ, Boston, MA 02215 USA

[12] NHLBIs Framingham Heart Study, Boston, MA USA

[13] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[14] Univ Bordeaux, CHU Bordeaux, Pole Sante Publ,CIC1401 EC, Inst Sante Publ Epidemiol & Dev,Ctr Inserm U1219, Bordeaux, France

[15] Univ Lille, CHU Lille, INSERM, Inst Pasteur Lille,U1167 RID Age LabEx DISTALZ Ri, F-59000 Lille, France

[16] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA

[17] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA

[18] Brigham & Womens Hosp, Div Aging, Dept Med, 75 Francis St, Boston, MA 02115 USA

[19] Harvard Med Sch, Boston, MA 02115 USA

[20] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA

[21] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[22] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[23] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[24] Univ Calif San Diego, Ctr Behav Genet Aging, La Jolla, CA 92093 USA

[25] Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA

[26] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA

[27] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA

[28] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[29] Monash Univ, Turner Inst Brain & Mental Hlth, Melbourne, Vic, Australia

[30] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[31] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[32] Boston Univ, Sch Med, Prevent Med & Epidemiol, Boston, MA 02118 USA

[33] Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France

[34] NIA, Baltimore, MD 21224 USA

[35] Univ Washington, Dept Neurol, Seattle, WA 98195 USA

来源：

COMMUNICATIONS BIOLOGY | 2022年 / 5卷 / 01期

关键词：

AMYLOID-BETA PEPTIDE; ALZHEIMERS-DISEASE; PLASMA TAU; CSF MARKERS; PROTEIN; DEMENTIA; PAR3; TRAFFICKING; BIOMARKERS; DIAGNOSIS;

D O I：

10.1038/s42003-022-03287-y

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. 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 x 10(-8). We additionally detected 14 novel loci at P < 5 x 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.

引用

页数：11

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