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Bipolar Disord. 2017 Mar;19(2):107-115. doi: 10.1111/bdi.12468. Epub 2017 Feb 23.

Serum phosphatidylinositol as a biomarker for bipolar disorder liability.

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Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Baker Heart and Diabetes Institute, Melbourne, Vic., Australia.
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Department of Genetics, University of Pennsylvania and Department of Biomedical and Health Informatics at Children's Hospital of Philadelphia, PA, USA.
Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.



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.


bipolar; family study; genetics; lipidome; phosphatidylinositol

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