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Brinkmeyer-Langford CL, Guan J, Ji G, et al. Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains. Front Aging Neurosci. 2016;8:183doi: 10.3389/fnagi.2016.00183.
Brinkmeyer-Langford, C. L., Guan, J., Ji, G., & Cai, J. J. (2016). Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains. Frontiers in aging neuroscience, 8183. https://doi.org/10.3389/fnagi.2016.00183
Brinkmeyer-Langford, Candice L, et al. "Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains." Frontiers in aging neuroscience vol. 8 (2016): 183. doi: https://doi.org/10.3389/fnagi.2016.00183
Brinkmeyer-Langford CL, Guan J, Ji G, Cai JJ. Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains. Front Aging Neurosci. 2016 Aug 03;8:183. doi: 10.3389/fnagi.2016.00183. eCollection 2016. PMID: 27536236; PMCID: PMC4971101.
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Front Aging Neurosci. 2016 Aug 03;8:183. doi: 10.3389/fnagi.2016.00183. eCollection 2016.

Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains.

Frontiers in aging neuroscience

Candice L Brinkmeyer-Langford, Jinting Guan, Guoli Ji, James J Cai

Affiliations

  1. Department of Veterinary Integrative Biosciences, Texas A&M University College Station, TX, USA.
  2. Department of Automation, Xiamen University Xiamen, China.
  3. Department of Automation, Xiamen UniversityXiamen, China; Innovation Center for Cell Signaling Network, Xiamen UniversityXiamen, China.
  4. Department of Veterinary Integrative Biosciences, Texas A&M UniversityCollege Station, TX, USA; Interdisciplinary Program in Genetics, Texas A&M UniversityCollege Station, TX, USA.

PMID: 27536236 PMCID: PMC4971101 DOI: 10.3389/fnagi.2016.00183

Abstract

Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases.

Keywords: Genotype-Tissue Expression (GTEx); brain transcriptome; expression dispersion; expression quantitative trait loci; factor analysis; gene expression; gene expression profiling; statistical

References

  1. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):137-47 - PubMed
  2. Nature. 2000 Mar 2;404(6773):99-103 - PubMed
  3. Neurobiol Aging. 2000 May-Jun;21(3):383-421 - PubMed
  4. Science. 2000 Jul 14;289(5477):304-6 - PubMed
  5. Mech Ageing Dev. 2001 Jan;122(1):1-29 - PubMed
  6. Immunogenetics. 2001 Jul;53(5):357-68 - PubMed
  7. J Neurosci. 2002 Nov 15;22(22):9800-9 - PubMed
  8. Eur J Immunol. 2003 Apr;33(4):1030-40 - PubMed
  9. Genome Biol. 2003;4(5):P3 - PubMed
  10. Science. 1963 Aug 23;141(3582):686-94 - PubMed
  11. Ann N Y Acad Sci. 1992 Dec 26;673:126-41 - PubMed
  12. PLoS Biol. 2004 May;2(5):E132 - PubMed
  13. BMC Med Genet. 2004 Jun 02;5:14 - PubMed
  14. Nature. 2004 Jun 24;429(6994):883-91 - PubMed
  15. Mech Ageing Dev. 2004 Oct-Nov;125(10-11):747-53 - PubMed
  16. Evolution. 2005 Jan;59(1):126-37 - PubMed
  17. PLoS Biol. 2005 Sep;3(9):e274 - PubMed
  18. Biometrics. 2006 Mar;62(1):245-53 - PubMed
  19. Proc Natl Acad Sci U S A. 1959 Jan;45(1):30-45 - PubMed
  20. Curr Biol. 2006 May 23;16(10):R359-60 - PubMed
  21. Nature. 2006 Jun 22;441(7096):1011-4 - PubMed
  22. Science. 2006 Oct 6;314(5796):130-3 - PubMed
  23. Neuroscience. 2007 Apr 14;145(4):1341-7 - PubMed
  24. PLoS One. 2007 Sep 12;2(9):e876 - PubMed
  25. PLoS Genet. 2007 Sep;3(9):1724-35 - PubMed
  26. Aging Cell. 2007 Dec;6(6):775-82 - PubMed
  27. Lancet Neurol. 2008 Jul;7(7):583-90 - PubMed
  28. Neuron. 2008 Sep 11;59(5):708-21 - PubMed
  29. Nat Neurosci. 2008 Nov;11(11):1271-82 - PubMed
  30. Toxicol Sci. 2009 Jan;107(1):281-92 - PubMed
  31. Brain. 1991 Oct;114 ( Pt 5):2283-301 - PubMed
  32. PLoS Genet. 2009 Dec;5(12):e1000776 - PubMed
  33. PLoS One. 2010 Mar 03;5(3):e9510 - PubMed
  34. FEBS Lett. 2011 Jul 7;585(13):2041-8 - PubMed
  35. PLoS Genet. 2011 Jan 20;7(1):e1001276 - PubMed
  36. Nat Genet. 2011 May;43(5):429-35 - PubMed
  37. Nat Genet. 2011 May;43(5):436-41 - PubMed
  38. Neurobiol Aging. 2011 Nov;32(11):2109.e15-28 - PubMed
  39. PLoS One. 2011;6(7):e21800 - PubMed
  40. PLoS Genet. 2011 Jul;7(7):e1002144 - PubMed
  41. Nature. 2011 Oct 26;478(7370):483-9 - PubMed
  42. Nat Protoc. 2012 Feb 16;7(3):500-7 - PubMed
  43. Neurobiol Dis. 2012 Jul;47(1):20-8 - PubMed
  44. Cell. 2012 Jun 8;149(6):1298-313 - PubMed
  45. Exp Mol Pathol. 2013 Feb;94(1):188-94 - PubMed
  46. Genetics. 2013 Jan;193(1):95-108 - PubMed
  47. Genome Biol. 2013 Jul 26;14(7):R75 - PubMed
  48. J Neurosci. 2013 Aug 14;33(33):13460-74 - PubMed
  49. Neurobiol Aging. 2014 Feb;35(2):279-90 - PubMed
  50. Nucleic Acids Res. 2014 Feb;42(4):2493-504 - PubMed
  51. Genetics. 2014 Feb;196(2):413-25 - PubMed
  52. Curr Opin Neurol. 2014 Apr;27(2):149-56 - PubMed
  53. Nature. 2014 Apr 10;508(7495):199-206 - PubMed
  54. Neurobiol Aging. 2014 Nov;35(11):2656.e1-2656.e7 - PubMed
  55. PLoS Genet. 2015 Jan 24;11(1):e1004942 - PubMed
  56. G3 (Bethesda). 2015 Mar 09;5(5):839-47 - PubMed
  57. Science. 2015 May 8;348(6235):648-60 - PubMed
  58. Nat Rev Neurosci. 2015 Jun;16(6):358-72 - PubMed
  59. J Neurochem. 2015 Sep;134(6):1026-39 - PubMed
  60. Nat Neurosci. 2015 Aug;18(8):1168-74 - PubMed
  61. Genome Biol. 2015 Sep 07;16:185 - PubMed
  62. Alzheimers Dement. 2016 Feb;12(2):121-129 - PubMed
  63. Sci Rep. 2015 Oct 19;5:15145 - PubMed
  64. Biopreserv Biobank. 2015 Oct;13(5):311-9 - PubMed
  65. Nat Commun. 2015 Oct 22;6:8570 - PubMed
  66. Immun Ageing. 2015 Nov 11;12:21 - PubMed
  67. Aging Cell. 2016 Apr;15(2):267-78 - PubMed
  68. Am J Hum Genet. 2016 Feb 4;98(2):299-309 - PubMed
  69. Science. 2016 May 6;352(6286):712-716 - PubMed
  70. Cell. 2016 May 5;165(4):1002-11 - PubMed
  71. Genome Biol. 2016 Apr 28;17:76 - PubMed
  72. Hum Mol Genet. 2016 Nov 15;25(22):4911-4919 - PubMed
  73. J Neuropathol Exp Neurol. 1985 Nov;44(6):559-77 - PubMed
  74. Science. 1985 Feb 15;227(4688):770-3 - PubMed
  75. Science. 1984 Sep 14;225(4667):1168-70 - PubMed
  76. Lancet. 1996 Jun 1;347(9014):1560 - PubMed
  77. J Biol Chem. 1997 Aug 15;272(33):20313-6 - PubMed
  78. Lancet. 1998 Feb 28;351(9103):645-6 - PubMed

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