The grant, Genetic Analysis of the International Cohort Collection for Bipolar Disorder, is continuation of a long-standing collaborative effort funded in response to an RFA for sample collections in bipolar disorder. We are thus submitting the current new application from the original group of investigators to continue the collaboration and proceed to its next logical step analyses of data being generated. We developed the International Cohort Collection for Bipolar Disorder in response to a NIMH FOA MH08-130. Under the auspices of R01MH085542 (Smoller/Sklar, PIs) and philanthropic funding we implemented a phenotypically robust, rapid, and cost effective method for sample collection. During the five years of the grant we have banked DNA from ~18,000 cases and 16,000 controls never previously used for genomic study of bipolar disorder (BD). We propose here enhanced aims in a unique sample to increase our knowledge of BD and to keep this highly productive team intact. The samples studied here will more than double the available samples for GWAS, and will be among the first to analyze rare variants using exome chip and exome sequencing. These analyses will provide substantially enhanced power for detection of networks and loci that confer BD risk.
In Aim 1 we will perform a genomic characterization of an independent cohort of 15,800 cases and 18,598 controls to identify high confidence genetic loci for risk of BD through association study of common single nucleotide polymorphisms, copy number variants, and rare single nucleotide variants. We will further use the data to explore genetic prediction models for BD for two specific clinical scenarios.
In Aim 2 we will apply these data to characterize the spectrum of genotype-phenotype relationships by examining phenotypic subgroups, cross- disorder relationships, quantitative personality dimensions, and neurocognition. Our goal is to learn more about the genetics of BD and how genes might act to alter disease risk. We propose to do this using the largest and most comprehensively studied sample collection in the field that includes both genetic and phenotypic risk factors.

Public Health Relevance

Bipolardisorderisadevastatingpsychiatricdiseasethataffectsmood.Itisfrequentlychronicanddisabling andverylittleisunderstoodaboutitsbiology.Inthisproposalwewilllearnmoreaboutthegeneticcausesof bipolardisordersothatwecanunderstandthebiologyanddevelopbettertreatmentsandmakebetter predictionsaboutclinicalcourse.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH106531-01
Application #
8861022
Study Section
Special Emphasis Panel (ZRG1-GGG-A (90))
Program Officer
Addington, Anjene M
Project Start
2015-04-15
Project End
2018-01-31
Budget Start
2015-04-15
Budget End
2016-01-31
Support Year
1
Fiscal Year
2015
Total Cost
$471,010
Indirect Cost
$157,957
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Goes, Fernando S; Pirooznia, Mehdi; Parla, Jennifer S et al. (2016) Exome Sequencing of Familial Bipolar Disorder. JAMA Psychiatry 73:590-7
Sellgren, C M; Kegel, M E; Bergen, S E et al. (2016) A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder. Mol Psychiatry 21:1342-50
Song, J; Bergen, S E; Di Florio, A et al. (2016) Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder. Mol Psychiatry 21:1290-7