title: Molecular sex differences in human serum.
abstract: BACKGROUND
  Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex.
  
  
  RESULTS
  Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic analyte expression in a cohort of 22 males and 22 females with Asperger syndrome. Reproducible sex differences were found in the levels of 77 analytes in serum of typical controls, and these comprised clusters of molecules enriched with distinct biological functions. Analytes involved in fatty acid oxidation/hormone regulation, immune cell growth and activation, and cell death were found at higher levels in females, and analytes involved in immune cell chemotaxis and other indistinct functions were higher in males. Comparison of these naturally occurring sex differences against a cohort of people with Asperger syndrome indicated that a cluster of analytes that had functions related to fatty acid oxidation/hormone regulation was associated with sex and the occurrence of this condition.
  
  
  CONCLUSIONS
  Sex-specific molecular differences were detected in serum of typical controls and these were reproducible across independent cohorts. This study extends current knowledge of sex differences in biological functions involved in metabolism and immune function. Deviations from typical sex differences were found in a cluster of molecules in Asperger syndrome. These findings illustrate the importance of investigating the influence of sex on medical conditions.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Ramsey
authors.forename: Emanuel
authors.initials: E
authors.lastname: Schwarz
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: Nico J M
authors.initials: NJ
authors.lastname: van Beveren
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.forename: Liliana
authors.initials: L
authors.lastname: Ruta
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D020817:Asperger Syndrome / Q000097:blood; D016000:Cluster Analysis; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D025341:Principal Component Analysis; D044967:Serum / Q000378:metabolism*; D012727:Sex Characteristics; D055815:Young Adult