title: Long-term exposure to black carbon, cognition and single nucleotide polymorphisms in microRNA processing genes in older men.
abstract: BACKGROUND
  Air pollution exposure has been linked to impaired cognitive aging, but little is known about biomarkers modifying this association. MicroRNAs (miRNAs) control gene expression and neuronal programming. miRNA levels vary due to single nucleotide polymorphisms (SNPs) in genes processing miRNAs from precursor molecules.
  
  
  OBJECTIVE
  To investigate whether SNPs in miRNA-processing genes are associated with cognition and modify the relationship between black carbon (BC), marker of traffic-related pollution, and cognitive functions.
  
  
  METHODS
  533 Normative Aging Study men (mean±SD 72±7years) were tested ≤4 times (mean=1.7 times) using seven cognitive tests between 1995 and 2007. We tested interactions of 16 miRNA-related SNPs with 1-year average BC from a validated land-use-regression model. We used covariate-adjusted logistic regression for low (≤25) Mini-Mental tate Examination (MMSE) and mixed-effect regression for a global cognitive score combining six other tests.
  
  
  RESULTS
  Global cognition was negatively associated with the homozygous minor variant of rs595961 AGO1 (-0.42SD; 95%CI: (-0.71, -0.13)) relative to the major variant. BC-MMSE association was stronger in heterozygous carriers of rs11077 XPO5 (OR=1.99; 95%CI: (1.39, 2.85)) and minor variant carriers of GEMIN4 rs2740348 (OR=1.34; 95%CI: (1.05, 1.7)), compared to their major variant. The BC-global-cognition association was stronger in heterozygous carriers of GEMIN4 rs4968104 (-0.10SD; 95%CI: (-0.18, -0.02)), and GEMIN4 rs910924 (-0.09SD; 95%CI: (-0.17, -0.02)) relative to the major variant. Blood miRNA expression analyses showed associations only of XPO5 rs11077 with miR-9 and miR-96.
  
  
  CONCLUSIONS
  Carriers of particular miRNA-processing SNPs had higher susceptibility to BC in BC-cognition associations, possibly due to influences on miRNA expression.
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: ecolicin@hsph.harvard.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: g.giuliano6@campus.unimib.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Giuliano
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: melinda.c.power@gmail.com.
authors.forename: Melinda C
authors.initials: MC
authors.lastname: Power
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: jlepeule@hsph.harvard.edu.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lepeule
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: ewilker@bidmc.harvard.edu.
authors.forename: Elissa H
authors.initials: EH
authors.lastname: Wilker
authors.affiliation: VA Boston Healthcare System and Boston University Schools of Public Health and Medicine, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: pantel.vokonas@va.gov.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: kbrennan@hsph.harvard.edu.
authors.forename: Kasey J M
authors.initials: KJM
authors.lastname: Brennan
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via Festa del Perdono, 7, 20122 Milano, Italy. Electronic address: sfossati@hsph.harvard.edu.
authors.forename: Serena
authors.initials: S
authors.lastname: Fossati
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono, 7, 20122 Milano, Italy; Epidemiology Unit, Department of Preventive Medicine, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza, 33, 20122 Milano, Italy. Electronic address: mirjam.hoxha@unimi.it.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.affiliation: VA Boston Healthcare System and Boston University Schools of Public Health and Medicine, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: aspiro3@bu.edu.
authors.forename: Avron
authors.initials: A
authors.lastname: Spiro
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: mweissko@hsph.harvard.edu.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: joel@hsph.harvard.edu.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: abaccare@hsph.harvard.edu.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000368:Aged; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects* / Q000032:analysis; D001900:Boston; D002244:Carbon / Q000032:analysis / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D053260:Soot / Q000032:analysis
chemical_list: D000393:Air Pollutants; D035683:MicroRNAs; D053260:Soot; D002244:Carbon
keywords: Air pollution; Black carbon; Cognitive function; MicroRNA; Single nucleotide polymorphisms