Request for Applications Post-Traumatic Stress Disorder GWAS

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Esmond Allison
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Request for Applications Post-Traumatic Stress Disorder GWAS PROGRAM OVERVIEW Cohen Veterans Bioscience & The Stanley Center for Psychiatric Research at the Broad Institute Collaboration are

1 Request for Applications Post-Traumatic Stress Disorder GWAS PROGRAM OVERVIEW Cohen Veterans Bioscience & The Stanley Center for Psychiatric Research at the Broad Institute Collaboration are supporting a large scale genome wide association study (GWAS) of Post- Traumatic Stress Disorder (PTSD), the PTSD Genetics Partnership in conjunction with the Psychiatric Genomics Consortium-Post-Traumatic Stress Disorder Working Group. Although PTSD can touch anyone in the wake of trauma, it is clear that a subsets of individuals are predisposed to PTSD, and also that PTSD is heritable in families. To uncover the genetic underpinnings of PTSD risk, the PTSD Genetics Partnership is calling for PTSD case and control samples from across the globe. To our knowledge, this will be the largest study of its kind in PTSD to date. We are seeking: 1. high-quality, DNA samples of PTSD cases as well as trauma exposed and ancestry matched controls. 2. Previously genotyped, legacy datasets to be used in the PGC meta-analysis. 3. Deep phenotypical data to accompany samples to allow for discovery of symptom-based patient clusters. We will support: genotyping, dataset integration, cleaning, and storage across research groups, and GWAS analysis for a target of 75K samples (25K cases, 50K controls). We invite: industry, academic, foundations and governmental entities to provide their retrospectively collected non-genotyped samples or genotyping data to join us in these efforts. All participating researchers will be asked to share their data across the PGC-PTSD Consortium and will be co-authors on the PGC-PTSD Cohen Veterans Bioscience Stanley Center at the Broad Institute GWAS Project 1 publication. We are seeking retrospective samples, that have already been collected and require genotyping, and genotyped samples which researchers would like to include in the metaanalysis. Please note that this funding will not support tissue and clinical data collection directly from patients.

2 BACKGROUND AND RATIONALE PTSD is a debilitating psychiatric disorder initiated by traumatic experience, with subsequent pathological re-experiencing, avoidance, numbing, and hyper-arousal symptoms. PTSD has a life-time prevalence of ~8% in the US making it among the most common psychiatric disorders. It occurs in up to 25% of subjects who have experienced severe psychological trauma, such as combat veterans, refugees, and assault victims. Genetic factors are critical in influencing who develops PTSD; heritability estimates for the disorder range from ~40-70% following trauma. However, robust genetic variants for PTSD have yet to be identified and the genetic architecture of PTSD remains largely unknown. To enable a large-scale GWAS of PTSD to be executed in the 2016 calendar year, the PTSD Genetics Partnership will compile genetic samples from PTSD cases and trauma exposed controls as well as deep phenotypical data from both groups. Both genotyped and nongenotyped samples that have already been collected from patients will be considered for inclusion in this request for applications. Cohen Veterans Bioscience and the Stanley Center for Psychiatric Research at the Broad Institute are funding the mission of the PGC-PTSD group in order to accomplish the critical next step in PTSD genetics: to conduct very large GWA studies of PTSD which can only be accomplished by large team science combining tens of thousands of samples across cohorts. By integrating phenotypical and genetic data across many researchers, this consortium hopes to identify risk loci for PTSD as well as identify the genetic underpinnings of intermediate phenotypes. CALL FOR APPLICATIONS Funds and support are available for the following: 1. Researchers who possess PTSD case and control extracted DNA to be genotyped and included in the meta-analysis. 2. PTSD case and control genetic and phenotypical data to be included in the metaanalysis. These samples have already been genotyped. 3. DNA extraction may be funded on a case-by-case basis. For existing tissue samples, we will sponsor PsychChip genotyping on the Illumina PsychChip array (or comparable Illumina platform) at the Broad Institute of high quality DNA samples, data QC, data storage and integration. To facilitate large-scale phenotypic analysis, we ask that as much phenotypic data as possible be included in addition to genetic data. Researchers will receive their genotyped data on scheduled release dates. For genotyped samples, we will support data cleaning and harmonization for integration into the larger PGC-PTSD dataset. To facilitate large-scale phenotypic analysis, we request that extensive phenotypic data be included in addition to genetic data. Phenotypic data collection is a high priority for this project. We will aid researchers with data cleaning and optimization for sharing within the consortium.

3 BENEFITS TO RESEARCHERS We anticipate several benefits to researchers: Researchers with existing, retrospective PTSD case and control samples will have their samples genotyped in the industrialized Genomics Platform of the Broad Institute, paid for by the PTSD Genetics Partnership. Researchers will acquire their genotyped, quality-controlled, cleaned, and imputed data back from the consortia in a timely manner. All researchers who contribute samples and/or retrospective legacy data will receive access to all data within the Project. Researchers will be part of a quarterly meeting with experts in the field of PTSD genetics. Semi-annual face to face meetings amongst PGC-PTSD consortium participants will be funded by the PTSD Genetics Partnership. Co-authorship on PGC-PTSD Phase 1 publications according to the authorship policy of the PGC-PTSD working group. On-site assistance for researchers may be provided for participants who require help with data submission, cleaning, and uploads to the server. EVALUATION PROCESS AND CONSIDERATIONS The following criteria will be prioritized for the selection of samples for genotyping: 1. Researcher s commitment to data sharing within the consortium 2. Cohort size 3. Sample availability date 4. Institutional willingness to share phenotypic data 5. Sample extraction occurred within the last 5 years 6. Researcher s commitment to provide all data by indicated deadlines The following will be required for application submission: 1. Date of sample availability 2. Tissue from which samples are derived 3. Sample status whether they are extracted and date of extraction 4. Dates of sample ascertainment 5. Availability of staff to ship samples and upload phenotypic data 6. Where current phenotypic data is stored 7. Phenotypic fields collected from patients, both cases and controls 8. Copies of informed consent for samples and phenotypic data 9. If your institution requires a Material Transfer Agreement (MTA), please include it with this application to expedite application processing and subsequent agreements Lastly, we suggest that researchers contact their IRBs to include the Broad Institute & Cohen Veterans Bioscience, if required by their institutions, upon application submission to expedite sample & data sharing process.

4 IMPORTANT DATES & DEADLINES Informational Overview Call #1: November 23, 2015 at 10am EST Informational Overview Call #2: December 1, 2015 at 11am EST Applications Due: December 11, 2015 Anticipated Award Announcement: January 11 th 2016 Face to Face Launch Meeting: week of February 8, 2016 DNA samples and phenotypical data required for submission: March 31, 2016 ELIGIBILITY REQUIREMENTS Applications may be submitted by: U.S. and non-u.s. biotechnology/pharmaceutical companies or other for-profit entities, either publicly or privately held, U.S. and non-u.s. entities, public and private non-profit entities, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the federal government. About Cohen Veterans Bioscience Cohen Veterans Bioscience is a 501(c)3 non-profit research organization dedicated to improving the detection and treatment of PTS and TBI and related co-morbidities through cutting-edge research, so the burden of these conditions may be lessened on service members, veterans, and their families. Through the generosity and support of Steven A. Cohen, we are launching translational research initiatives in Post-Traumatic Stress Disorder and Traumatic Brain Injury. To ensure the future holds improved care for veterans, we seek to assemble high-dimensional biomarker, biosensor, and phenotypic data to build predictive models of disease and accelerate the time to next generation diagnostics and treatments. About the Stanley Center for Psychiatric Research at Broad Institute The mission of the Stanley Center for Psychiatric Research at the Broad Institute is to reduce the burden of serious mental illness through research. Stanley Center researchers focus on schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder, and other neuropsychiatric disorders. Situated within the Broad Institute of MIT and Harvard, the Stanley Center aims to exploit the most advanced technologies for human genetic analysis to study these psychiatric disorders in order to understand disease mechanisms, identify potential biomarkers, and ignite needed progress in therapeutics. Launched in 2007 by a $100 million commitment from the Stanley Medical Research Institute, the Stanley Center has extensive collaborations with investigators at MIT, Harvard, and the Harvard-affiliated hospitals as well as with investigators around the world.

5 About the Psychiatric Genomics Consortium - PTSD Working Group The PGC was established in 2007 to conduct field-wide mega-analyses of individual data for attention-deficit hyperactivity disorder, autism spectrum disorders, bipolar disorder, Major depression disorder, and schizophrenia. In the past 2 years, PTSD, OCD/Tourette s, anorexia nervosa, and drug use disorders groups have been added. The PGC, which united the field for the first time as an enormous consortium (500+ scientists from 80+ institutions in 25 countries), has already produced three major findings of genetic architecture for psychiatric disorders.

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