title: Serum phosphatidylinositol as a biomarker for bipolar disorder liability.
abstract: Individuals with bipolar disorder (BPD) exhibit alterations in their phospholipid levels. It is unclear whether these alterations are a secondary consequence of illness state, or if phospholipids and illness risk overlap genetically. If the latter were true, then phospholipids might provide key insights into the pathophysiology of the illness. Therefore, we rank-ordered phospholipid classes by their genetic overlap with BPD risk in order to establish which class might be most informative in terms of increasing our understanding of illness pathophysiology.
  
  
  
  Analyses were conducted in a sample of 558 individuals, unselected for BPD, from 38 extended pedigrees (average family size=14.79, range=2-82). We calculated a coefficient of relatedness for all family members of nine individuals with BPD in the sample (N=185); this coefficient was set to be zero in unrelated individuals (N=373). Then, under an endophenotype ranking value (ERV) approach, this scalar index was tested against 13 serum-based phospholipid concentrations in order to rank-order lipid classes by their respective overlap with BPD risk.
  
  
  
  The phosphatidylinositol class was significantly heritable (h2=0.26, P=6.71 × 10-05). It was the top-ranked class, and was significantly associated with BPD risk after correction for multiple testing (β=-1.18, P=2.10 × 10-03, ERV=0.49).
  
  
  
  We identified a peripheral biomarker, serum-based phosphatidylinositol, which exhibits a significant association with BPD risk. Therefore, given that phosphatidylinositol and BPD risk share partially common etiology, it seems that this lipid class warrants further investigation, not only in terms of treatment, but also as a promising diagnostic and risk marker.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Emma Em
authors.identifier: 0000-0003-0642-267X
authors.initials: EE
authors.lastname: Knowles
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Vic., Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Vic., Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Huynh
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: Harald Hh
authors.initials: HH
authors.lastname: Göring
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Rene L
authors.initials: RL
authors.lastname: Olvera
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Mathias
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: Department of Genetics, University of Pennsylvania and Department of Biomedical and Health Informatics at Children's Hospital of Philadelphia, PA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000235:genetics; D058068:Endophenotypes / Q000032:analysis; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010716:Phosphatidylinositols / Q000097:blood*; D011569:Psychiatric Status Rating Scales; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D010716:Phosphatidylinositols
keywords: bipolar; family study; genetics; lipidome; phosphatidylinositol