A genetic study of cerebral atherosclerosis reveals novel associations with ntng1 and cnot3
De Jager, P.L.
AffiliationBanner Alzheimer’s Institute, Arizona State University and University of Arizona
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CitationVattathil, S. M., Liu, Y., Harerimana, N. V., Lori, A., Gerasimov, E. S., Beach, T. G., Reiman, E. M., De Jager, P. L., Schneider, J. A., Bennett, D. A., Seyfried, N. T., Levey, A. I., Wingo, A. P., & Wingo, T. S. (2021). A genetic study of cerebral atherosclerosis reveals novel associations with ntng1 and cnot3. Genes, 12(6).
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AbstractCerebral atherosclerosis is a leading cause of stroke and an important contributor to dementia. Yet little is known about its genetic basis. To examine the association of common single nucleotide polymorphisms with cerebral atherosclerosis severity, we conducted a genomewide association study (GWAS) using data collected as part of two community-based cohort studies in the United States, the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). Both studies enroll older individuals and exclude participants with signs of dementia at baseline. From our analysis of 1325 participants of European ancestry who had genotype and neuropathologically assessed cerebral atherosclerosis measures available, we found a novel locus for cerebral atherosclerosis in NTNG1. The locus comprises eight SNPs, including two independent significant SNPs: rs6664221 (β = −0.27, 95% CI = (−0.35, −0.19), p = 1.29 × 10−10 ) and rs10881463 (β = −0.20, 95% CI = (−0.27, −0.13), p = 3.40 × 10−8 ). We further found that the SNPs may influence cerebral atherosclerosis by regulating brain protein expression of CNOT3. CNOT3 is a subunit of CCR4−NOT, which has been shown to be a master regulator of mRNA stability and translation and an important complex for cholesterol homeostasis. In summary, we identify a novel genetic locus for cerebral atherosclerosis and a potential mechanism linking this variation to cerebral atherosclerosis progression. These findings offer insights into the genetic effects on cerebral atherosclerosis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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Except where otherwise noted, this item's license is described as Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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- Issue date: 2016 Aug
- Expression quantitative trait locus fine mapping of the 17q12-21 asthma locus in African American children: a genetic association and gene expression study.
- Authors: Ober C, McKennan CG, Magnaye KM, Altman MC, Washington C 3rd, Stanhope C, Naughton KA, Rosasco MG, Bacharier LB, Billheimer D, Gold DR, Gress L, Hartert T, Havstad S, Khurana Hershey GK, Hallmark B, Hogarth DK, Jackson DJ, Johnson CC, Kattan M, Lemanske RF, Lynch SV, Mendonca EA, Miller RL, Naureckas ET, O'Connor GT, Seroogy CM, Wegienka G, White SR, Wood RA, Wright AL, Zoratti EM, Martinez FD, Ownby D, Nicolae DL, Levin AM, Gern JE, Environmental Influences on Child Health Outcomes-Children's Respiratory Research Workgroup.
- Issue date: 2020 May
- Genome-wide Meta-analysis on the Sense of Smell Among US Older Adults.
- Authors: Dong J, Yang J, Tranah G, Franceschini N, Parimi N, Alkorta-Aranburu G, Xu Z, Alonso A, Cummings SR, Fornage M, Huang X, Kritchevsky S, Liu Y, London S, Niu L, Wilson RS, De Jager PL, Yu L, Singleton AB, Harris T, Mosley TH Jr, Pinto JM, Bennett DA, Chen H
- Issue date: 2015 Nov
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- Issue date: 2019 Oct 1