Severe Mental Illness: From Polygenicity to Biology

This two-day symposium, chaired by Steve Hyman, Guoping Feng and Ben Neale, brought together leading scientists working on the genetics, neurobiology, and treatment of schizophrenia, bipolar disorder, autism spectrum disorder, and related neuropsychiatric disorders.

The central theme this year was addressing the challenges of turning genetic results that reveal extreme polygenicity into useful biological insights that can help patients. Graduate students and postdoctoral associates are especially welcomed to this symposium in order to build this interdisciplinary field and address the unmet medical needs of patients and their families at a time of great opportunity and urgency.

All sessions were held in the auditorium of the Broad Institute, 415 Main Street, Cambridge MA 02142.

Agenda Day 1 Monday, September 16, 2019
Session 1: Genetics: Setting the Problem, revealing the challenge Chair: Ben Neale
8:15 – 8:50 Breakfast in Lobby 8:50 – 9:00 Welcome Steve Hyman Broad Institute 9:00 – 9:10 Session Introduction Ben Neale Massachusetts General Hospital/Broad Institute 9:10 – 9:40 Common genetic variants associated with Schizophrenia: a Psychiatric Genomics Consortium (PGC) collaboration Stephan Ripke Charité University/Massachusetts General Hospital 9:40 – 10:10 Leveraging polygenicity for biological insight from genome-wide association data Hilary Finucane Broad Institute 10:10 – 10:40 ENIGMA at 10: What have we learned from a decade of large scale collaborative meta-analysis in neuroimaging Sarah Medland QIMR Berghofer 10:40 – 11:00 Coffee Break 11:00 – 11:30 Adaptively using auxiliary data to discover risk genes provides powerful insights into mental illnesses Kathryn Roeder Carnegie Mellon University 11:30 – 12:00 Interpreting genetic associations with detailed human behavioral data Elise Robinson Harvard T.H. Chan School of Public Health/Broad Institute 12:00 – 12:45 Panel Discussion: How do we put the genetics to work Randy Buckner, Alicia Martin, Ken Kendler, Kevin Eggan, Anji Addington 12:45 – 1:15 Lunch
Short talks selected from submitted abstracts
1:15 – 1:20 Intro to short talks Guoping Feng MIT/Broad Institute 1:20 – 1:35 Short Talk I Silvia Velasco Harvard University/Stanley Center for Psychiatric Research 1:35 – 1:50 Short Talk II Richard Smith Boston Children’s Hospital/Harvard Medical School
Session 2: Clinical Translation: phenotyping and patient stratification Chair: Morgan Sheng
1:50 – 2:00 Session Introduction Morgan Sheng Broad Institute 2:00 – 2:30 Clinical utility of polygenic risk for prediction in high risk populations Carrie Bearden UCLA 2:30 – 3:00 Using fluid biomarkers to investigate brain disorders Henrik Zetterberg University of Gothenburg 3:00 – 3:20 Coffee Break 3:20 – 3:50 Primary prevention of brain disease Eric Minikel & Sonia Vallabh Broad Institute 3:50 – 4:20 Patient selection strategies for clinical trails in monogenic and complex neurological disease Sally John Biogen 4:20 – 4:50 Designing Imaging Biomarkers for Microglia States Flo Wagner Broad Institute & Beth Stevens Boston Children’s Hospital/Broad Institute 4:50 – 5:00 Closing remarks from session chair
Poster Session & Reception
5:15 – 7:00 McGovern Institute Atrium

Day 2 Tuesday, September 17, 2019
Session 3: Enabling Technologies Chair: Evan Macosko
8:15 – 8:50 Breakfast in Lobby 8:50 – 9:00 Session Introduction Evan Macosko Harvard Medical School/Broad Institute 9:00 – 9:30 Dissecting Neural Circuits Across Model Systems with Cell Type and Single Cell Resolution Ed Callaway Salk Institute 9:30 – 10:00 Single-cell transcriptome imaging and cell atlas of brain tissues Xiaowei Zhuang Harvard University 10:00 – 10:20 Coffee Break 10:20 – 10:50 The circuit dynamics of brain states Karl Deisseroth Stanford University 10:50 – 11:20 Analyzing animal behavior using machine vision and learning Kristin Branson Janelia Research Campus 11:20 – 11:30 3 Teaser talks for poster session #2 Tarjinder Singh Massachusetts General Hospital Stanley Center for Psychiatric Research on behalf of the SCHEMA consortium 11:30 – 11:40 ChangHui Pak Stanford University University of Massachusetts Amherst 11:40 – 11:50 Seth Hopkins Sunovion Pharmaceuticals Inc. 11:50 – 1:00 Lunch and poster session round 2
Keynote
1:00 – 1:05 Keynote Introduction Steve Hyman 1:05 – 2:00 Keynote: Our restless brains - Exploring the universe within Marcus Raichle Washington University in St Louis
Session 4: Biology enabled by new models Chair: Paola Arlotta
2:00 – 2:10 Session Introduction Paola Arlotta Harvard University/Broad Institute 2:10 – 2:50 Coupling Genotype to Phenotype: Genetic Buffering, Homeostatic Plasticity and a Phenotypic Spectrum Grae Davis UCSF 2:50 – 3:20 Translating genetic risk of Alzheimer’s disease into mechanisms of disease Bart de Strooper VIB-KU Leuven 3:20 – 3:40 Dissecting mechanisms of FMRP in RNA processing using human stem cell models Lindy Barrett Broad Institute 3:40 – 4:00 Coffee Break 4:00 – 4:20 Innovations in Primate Interneuron Repertoire Fenna Krienen Broad Institute 4:20 – 4:50 Conservation and divergence of human brain cell types Ed Lein Allen Institute 4:50 – 5:20 Taking Stock: Where do we go from here? Paola Arlotta, Carrie Bearden, Karl Deisseroth, Steve McCarroll, Marcus Raichle 5:20 – 5:30 Concluding remarks from symposium chairs