Chen, J;
Yu, J-T;
Wojta, K;
Wang, H-F;
Zetterberg, H;
Blennow, K;
Yokoyama, JS;
... Boxer, AL; + view all
(2017)
Genome-wide association study identifies MAPT locus influencing human plasma tau levels.
Neurology
, 88
(7)
pp. 669-676.
10.1212/WNL.0000000000003615.
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Abstract
OBJECTIVE: To identify genetic loci associated with plasma tau concentrations in healthy elders and individuals with Alzheimer disease. METHODS: Four hundred sixty-three non-Hispanic white individuals exceeding quality control criteria were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort. Association of plasma tau with genetic polymorphisms was performed with a linear regression model. Significant associations were validated in an independent replication cohort consisting of 431 healthy elders or individuals with mild cognitive impairment recruited from the University of California, San Francisco Memory and Aging Center. RESULTS: The minor allele (A) of rs242557 in the microtubule-associated protein tau gene (MAPT) was associated with higher plasma tau levels at genome-wide significance (p = 4.85 × 10−9, empiric family-wise error corrected p = 0.0024) in a dose-dependent fashion. This association was also observed in the replication cohort (p = 1.0 × 10−5; joint analysis p = 1.2 × 10−12). Single nucleotide polymorphisms near PARK2 (rs2187213) (p = 6.15 × 10−6), IL2RA (rs7072793, rs7073236) (p = 7.89 × 10−6), and an intergenic locus on 9p21.3 (rs7047280) (p = 8.13 × 10−6) were identified as suggestive loci associated with plasma tau levels. CONCLUSIONS: MAPT H1c haplotype (rs242557) has previously been identified as a genetic risk factor for progressive supranuclear palsy and corticobasal degeneration. The current findings suggest that plasma tau concentration could be an endophenotype for identifying risk for 4-repeat tauopathies in older individuals.
| Type: | Article |
|---|---|
| Title: | Genome-wide association study identifies MAPT locus influencing human plasma tau levels |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/WNL.0000000000003615 |
| Publisher version: | http://doi.org/10.1212/WNL.0000000000003615 |
| Language: | English |
| Additional information: | © 2017 American Academy of Neurology. This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, PROGRESSIVE SUPRANUCLEAR PALSY, CEREBROSPINAL-FLUID, ALZHEIMERS-DISEASE, CORTICOBASAL DEGENERATION, GENE-EXPRESSION, RISK VARIANTS, HAPLOTYPE, TAUOPATHIES, MUTATIONS, REGION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1551087 |
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