Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
    • Subject Terms:
      Alzheimer Disease/*cerebrospinal fluid ; Cerebrospinal Fluid/*metabolism ; Cognitive Dysfunction/*cerebrospinal fluid; Aged ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Brain/metabolism ; Case-Control Studies ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/metabolism ; Cohort Studies ; Female ; Genome-Wide Association Study ; Humans ; Male ; Metabolomics/methods ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci
    • Abstract:
      The study of metabolomics and disease has enabled the discovery of new risk factors, diagnostic markers, and drug targets. For neurological and psychiatric phenotypes, the cerebrospinal fluid (CSF) is of particular importance. However, the CSF metabolome is difficult to study on a large scale due to the relative complexity of the procedure needed to collect the fluid. Here, we present a metabolome-wide association study (MWAS), which uses genetic and metabolomic data to impute metabolites into large samples with genome-wide association summary statistics. We conduct a metabolome-wide, genome-wide association analysis with 338 CSF metabolites, identifying 16 genotype-metabolite associations (metabolite quantitative trait loci, or mQTLs). We then build prediction models for all available CSF metabolites and test for associations with 27 neurological and psychiatric phenotypes, identifying 19 significant CSF metabolite-phenotype associations. Our results demonstrate the feasibility of MWAS to study omic data in scarce sample types.
    • References:
      PLoS Genet. 2016 Aug 05;12(8):e1006125. (PMID: 27494321)
      Curr Opin Neurobiol. 2020 Apr;61:29-39. (PMID: 31838254)
      Am J Psychiatry. 2013 Apr;170(4):372-82. (PMID: 23223954)
      Am J Hum Genet. 2007 Sep;81(3):559-75. (PMID: 17701901)
      Nat Rev Drug Discov. 2016 Jul;15(7):473-84. (PMID: 26965202)
      Genet Epidemiol. 2016 May;40(4):304-14. (PMID: 27061298)
      Nature. 2011 Aug 31;477(7362):54-60. (PMID: 21886157)
      Nat Genet. 2016 Mar;48(3):245-52. (PMID: 26854917)
      Alzheimers Dement (Amst). 2017 Dec 08;10:130-142. (PMID: 29322089)
      Nat Genet. 2020 Feb;52(2):167-176. (PMID: 31959995)
      J Alzheimers Dis. 2015;50(3):873-86. (PMID: 26836182)
      Nat Commun. 2018 Jan 23;9(1):333. (PMID: 29362361)
      Sci Signal. 2020 Mar 24;13(624):. (PMID: 32209698)
      Cell. 2008 Nov 28;135(5):813-24. (PMID: 19041747)
      J Stat Softw. 2010;33(1):1-22. (PMID: 20808728)
      Cell. 2008 Sep 19;134(6):933-44. (PMID: 18805087)
      PLoS Genet. 2015 Sep 09;11(9):e1005487. (PMID: 26352407)
      Nat Genet. 2016 Oct;48(10):1279-83. (PMID: 27548312)
      Genet Epidemiol. 2019 Sep;43(6):657-674. (PMID: 31104335)
      Mol Psychiatry. 2007 Oct;12(10):934-45. (PMID: 17440431)
      Nat Genet. 2017 Apr;49(4):568-578. (PMID: 28263315)
      Biol Res Nurs. 2018 May;20(3):352-358. (PMID: 29514460)
      Mol Genet Metab. 2012 Aug;106(4):430-8. (PMID: 22728054)
      Nat Genet. 2014 Jun;46(6):543-550. (PMID: 24816252)
      Nat Neurosci. 2019 Jul;22(7):1066-1074. (PMID: 31209380)
      Nat Genet. 2019 Mar;51(3):431-444. (PMID: 30804558)
      PLoS One. 2013 Jul 24;8(7):e68717. (PMID: 23894336)
      Nature. 2009 Feb 12;457(7231):910-4. (PMID: 19212411)
      Bioinformatics. 2015 May 1;31(9):1466-8. (PMID: 25550326)
      Cell. 2014 Oct 9;159(2):318-32. (PMID: 25303528)
      Clin Cancer Res. 2007 Nov 1;13(21):6359-68. (PMID: 17975148)
      Nat Genet. 2011 Jun;43(6):565-9. (PMID: 21572414)
      Nat Rev Neurol. 2010 Mar;6(3):131-44. (PMID: 20157306)
      Nat Genet. 2016 Oct;48(10):1284-1287. (PMID: 27571263)
      Bioinformatics. 2014 Oct 15;30(20):2906-14. (PMID: 24990607)
      Alzheimers Dement. 2011 May;7(3):257-62. (PMID: 21514247)
      Elife. 2018 May 30;7:. (PMID: 29846171)
      Lancet Neurol. 2019 Dec;18(12):1091-1102. (PMID: 31701892)
      Nat Genet. 2018 May;50(5):668-681. (PMID: 29700475)
      Bioinformatics. 2020 Jan 15;36(2):649-650. (PMID: 31373609)
      Nat Genet. 2019 Jan;51(1):63-75. (PMID: 30478444)
      PLoS Genet. 2013 Mar;9(3):e1003348. (PMID: 23555274)
      PLoS Genet. 2012;8(10):e1003005. (PMID: 23093944)
      Nature. 2014 Jul 24;511(7510):421-7. (PMID: 25056061)
      Nat Commun. 2017 Sep 20;8(1):611. (PMID: 28931804)
      Am J Psychiatry. 2019 Mar 1;176(3):217-227. (PMID: 30818990)
      J Neuroimmune Pharmacol. 2015 Sep;10(3):425-34. (PMID: 25850894)
      PLoS One. 2010 Nov 11;5(11):e13953. (PMID: 21085649)
      Mol Psychiatry. 2018 May;23(5):1181-1188. (PMID: 28761083)
      Mol Psychiatry. 2014 Feb;19(2):228-34. (PMID: 23319000)
      Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. (PMID: 30395287)
      Nat Commun. 2019 Oct 8;10(1):4558. (PMID: 31594949)
      Int J Epidemiol. 2015 Apr;44(2):512-25. (PMID: 26050253)
      Schizophr Bull. 2020 Jul 8;46(4):804-813. (PMID: 31919502)
      Nucleic Acids Res. 2018 Jan 4;46(D1):D608-D617. (PMID: 29140435)
      Nat Genet. 2019 Apr;51(4):592-599. (PMID: 30926968)
      Neuropsychiatr Dis Treat. 2006 Dec;2(4):531-6. (PMID: 19412501)
      Nat Genet. 2013 Jun;45(6):580-5. (PMID: 23715323)
      Nat Commun. 2017 Jan 18;8:13624. (PMID: 28098162)
      Cell Metab. 2009 Apr;9(4):311-26. (PMID: 19356713)
      Nat Genet. 2018 Apr;50(4):538-548. (PMID: 29632383)
      Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012. (PMID: 30445434)
      Psychiatry Res. 2019 Feb;272:18-29. (PMID: 30579177)
      PLoS Genet. 2014 Feb 20;10(2):e1004132. (PMID: 24586186)
      Bioinformatics. 2010 Sep 1;26(17):2190-1. (PMID: 20616382)
      Dialogues Clin Neurosci. 2011;13(3):251-62. (PMID: 22034252)
      Nat Genet. 2018 Mar;50(3):381-389. (PMID: 29483656)
      Nat Genet. 2016 Jun;48(6):624-33. (PMID: 27089181)
      Elife. 2024 May 24;12:. (PMID: 38787369)
      Nat Genet. 2012 Jan 29;44(3):269-76. (PMID: 22286219)
      Hum Mol Genet. 2017 Jan 1;26(1):44-51. (PMID: 28031287)
      J Alzheimers Dis. 2016 Nov 19;55(2):473-484. (PMID: 27662287)
      Nat Genet. 2018 Aug;50(8):1112-1121. (PMID: 30038396)
      Psychiatry Res. 2019 Feb;272:36-41. (PMID: 30579179)
      Nat Genet. 2019 May;51(5):793-803. (PMID: 31043756)
      Neurology. 1984 Jul;34(7):939-44. (PMID: 6610841)
      J Alzheimers Dis. 2018;66(2):751-773. (PMID: 30347620)
      JAMA Psychiatry. 2019 Sep 1;76(9):924-932. (PMID: 31116379)
      Lancet Neurol. 2014 Sep;13(9):893-903. (PMID: 25087078)
      Electrophoresis. 2008 Jul;29(13):2884-90. (PMID: 18512679)
      Hum Mol Genet. 2020 Mar 27;29(5):864-875. (PMID: 31960908)
      Nat Genet. 2019 Mar;51(3):568-576. (PMID: 30804563)
      Mol Psychiatry. 2020 Oct;25(10):2410-2421. (PMID: 30116032)
      Laryngoscope. 2017 Jul;127(7):E244-E250. (PMID: 28000217)
      Am J Physiol Renal Physiol. 2014 Dec 15;307(12):F1373-9. (PMID: 25354943)
      Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773. (PMID: 30357393)
      Hum Mol Genet. 2012 Aug 15;21(16):3719-26. (PMID: 22595970)
      PLoS Genet. 2011 Sep;7(9):e1002270. (PMID: 21931564)
      PLoS One. 2013 May 20;8(5):e63644. (PMID: 23700429)
      Nat Genet. 2019 Aug;51(8):1207-1214. (PMID: 31308545)
      Bioinformatics. 2010 Sep 15;26(18):2336-7. (PMID: 20634204)
      PLoS Genet. 2014 Mar 13;10(3):e1004212. (PMID: 24625756)
      Nature. 2011 Apr 7;472(7341):57-63. (PMID: 21475195)
      Nat Genet. 2016 Nov;48(11):1443-1448. (PMID: 27694958)
      Nat Genet. 2019 Mar;51(3):404-413. (PMID: 30617256)
      J Proteome Res. 2011 Oct 7;10(10):4769-88. (PMID: 21823675)
      Nat Genet. 2015 Sep;47(9):1091-8. (PMID: 26258848)
      Nat Neurosci. 2016 Dec;19(12):1569-1582. (PMID: 27694991)
      Nat Commun. 2018 Jul 3;9(1):2457. (PMID: 29970889)
      Bioinformatics. 2018 Dec 15;34(24):4313-4314. (PMID: 29955821)
      Clin Cancer Res. 2017 Mar 1;23(5):1227-1235. (PMID: 27582484)
      Genome Biol. 2021 Sep 6;22(1):257. (PMID: 34488838)
      Nat Commun. 2016 Jan 29;7:10558. (PMID: 26822151)
      Nat Genet. 2019 Feb;51(2):237-244. (PMID: 30643251)
      Schizophr Res. 2017 May;183:70-74. (PMID: 27856156)
      Neuroimage. 2017 Oct 1;159:159-169. (PMID: 28736311)
      Sci Adv. 2016 Aug 31;2(8):e1600800. (PMID: 27602404)
      BMC Med. 2011 Apr 18;9:40. (PMID: 21501494)
    • Grant Information:
      R01 AG037639 United States AG NIA NIH HHS; UL1 TR000427 United States TR NCATS NIH HHS; T15 LM007359 United States LM NLM NIH HHS; T32 LM012413 United States LM NLM NIH HHS; RF1 AG027161 United States AG NIA NIH HHS; T32 AG000213 United States AG NIA NIH HHS; P2C HD047873 United States HD NICHD NIH HHS; UL1 TR002373 United States TR NCATS NIH HHS; P30 AG062715 United States AG NIA NIH HHS; P50 AG033514 United States AG NIA NIH HHS; R01 AG027161 United States AG NIA NIH HHS; R01 AG054047 United States AG NIA NIH HHS; P30 AG017266 United States AG NIA NIH HHS; R21 AG067092 United States AG NIA NIH HHS
    • Publication Date:
      Date Created: 20210113 Date Completed: 20210709 Latest Revision: 20241003
    • Publication Date:
      20241003
    • Accession Number:
      PMC7803963
    • Accession Number:
      10.1038/s42003-020-01583-z
    • Accession Number:
      33437055