title: Progranulin gene variation affects serum progranulin levels differently in Danish bipolar individuals compared with healthy controls.
abstract: The identification of peripheral biomarkers for bipolar disorder is of great importance and has the potential to improve diagnosis, treatment and prognosis. Recent studies have reported lower plasma progranulin levels in bipolar individuals compared with controls and association with single nucleotide polymorphisms (SNPs) within the progranulin gene (GRN). In the present study, we investigated the effect of GRN and sortilin (SORT1) gene variation on serum progranulin levels in bipolar individuals and controls.
  
  
  
  In a Danish cohort of individuals with bipolar disorder and controls, we analysed the serum progranulin level (nbipolar=80, ncontrols=76) and five SNPs located within GRN and two SNPs near the SORT1 gene encoding sortilin, a progranulin scavenger receptor known to affect circulating progranulin levels (nbipolar=166, ncontrols=186).
  
  
  
  We observed no significant difference in the serum progranulin level between cases and controls and none of the analysed SNPs located within GRN or close to SORT1 were associated with bipolar disorder. Crude and adjusted (adjusted for case-control status, sex and age) linear regression analyses showed no effect of any SNPs on the serum progranulin level. However, we observed that the mean serum progranulin level in cases and controls is affected differently depending on the genotypes of two SNPs within GRN (rs2879096 and rs4792938).
  
  
  
  The sample size is relatively small and detailed information on medication and polarity of the disorder is not available. No correction for multiple testing was performed.
  
  
  
  Our study suggests that the potential of progranulin as a biomarker for bipolar disorder is genotype dependent.
authors.affiliation: aTranslational Neuropsychiatry Unit, Department of Clinical Medicine bDepartment of Biomedicine, The Lundbeck Foundation Research Center, MIND cDepartment of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University dDepartment of Psychosis, Psychosis Research Unit, Aarhus University Hospital, Risskov eThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark fDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Henriette N
authors.initials: HN
authors.lastname: Buttenschøn
authors.forename: Marit N
authors.initials: MN
authors.lastname: Nielsen
authors.forename: Gangadaar
authors.initials: G
authors.lastname: Thotakura
authors.forename: Chris W
authors.initials: CW
authors.lastname: Lee
authors.forename: Anders
authors.initials: A
authors.lastname: Nykjær
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Simon
authors.initials: S
authors.lastname: Glerup
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000077153:Progranulins; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D000099183:Sortilin; C492314:GRN protein, human