title: Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study.
abstract: BACKGROUND
  Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP).
  
  
  METHODS
  Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest.
  
  
  RESULTS
  After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters.
  
  
  CONCLUSIONS
  These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. sabine.ameling@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. sabine.ameling@uni-greifswald.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ameling
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. tim.kacprowski@uni-greifswald.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Kacprowski
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. ravikumar.ch@gmail.com.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Chilukoti
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. carolin_malsch@live.de.
authors.forename: Carolin
authors.initials: C
authors.lastname: Malsch
authors.affiliation: Institute of Mathematics and Informatics, Ernst-Moritz-Arndt-University, Greifswald, Germany. volkmar.liebscher@uni-greifswald.de.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Liebscher
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, PO Box 24144, Doha, Qatar. karsten@suhre.fr.|Helmholtz Zentrum München, Germany, Research Centre for Environmental Health, Neuherberg, Germany. karsten@suhre.fr.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. maik.pietzner@uni-greifswald.de.
authors.forename: Maik
authors.initials: M
authors.lastname: Pietzner
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. nele.friedrich@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. nele.friedrich@uni-greifswald.de.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. georg.homuth@uni-greifswald.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. hammer@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. hammer@uni-greifswald.de.
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, , Friedrich-Ludwig-Jahn-Str. 15A, D-17475, Greifswald, Germany. voelker@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. voelker@uni-greifswald.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood* / Q000235:genetics; D001773:Blood Cells / Q000378:metabolism; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010641:Phenotype; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D035683:MicroRNAs