Update on the Million Veteran Program Opportunities for Collaboration with WHI T. L. Assimes, MD PhD FAHA

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1 Update on the Million Veteran Program Opportunities for Collaboration with WHI T. L. Assimes, MD PhD FAHA Associate Professor of Medicine, Stanford University Associate Director, Palo Alto VA Health Care Attending Research and Information Center for Genomics, Palo Alto VA Hospital WHI Annual Investigators Meeting, Chicago, May 4, 2018

Genetic Research in the VA Ideal setting for mega-cohort and pop.

infrastructure with diverse expertise Altruistic pool of participants ~22 million

integrated EHR Ancillary health data: fee for service file for emergencies outside

2 Genetic Research in the VA Ideal setting for mega-cohort and pop. based biobank Largest integrated healthcare system in nation embedded research infrastructure with diverse expertise Altruistic pool of participants ~22 million Veterans ~9 million enrolled in VHA ~6 million using regularly Oldest fully integrated EHR Ancillary health data: fee for service file for emergencies outside of VA linkage to CMS, and NDI Million Veteran Program (MVP) recruitment launched 2011 by VHA Central Office of R & D

3 Current MVP Enrollment Sites TOTAL: 152 VA Medical Centers, ~1400 VA Community-Based Outpatient Clinics

4 MVP Enrollment criterion Any Veteran enrolled in VA Health Care System and receiving care at a participating VAMC Voluntary, no effect on access to health care or benefits No other inclusions / exclusion criterion Participation involves: 1. Up to 2 short surveys 2. one-time study visit to provide a blood sample (one 10 ml tube) 3. ongoing access to medical records 4. Possible future contact

5 Baseline Survey MVP Surveys Demographics, physical features (eye color, hair color, etc.), military experience general lifestyle habits, health status, medical history, family history healthcare usage Lifestyle Survey exercise & dietary habits, mental health military and environmental exposure men/women s health medication usage

7 MVP Enrollees: Age and Gender VHA Population MVP Enrollees (n=145,270)

8 MVP Self Report of Race/Ethnicity on Baseline Survey Demographically representative of users of the VA Health Care System 8

9 MVP: Self-Reported Conditions (n=357,358) Condition N Percent hypertension 220, % high cholesterol 197, % depression 100, % diabetes 94, % sleep apnea 89, % colonic polyps 76, % enlarged prostate 67, % PTSD 66, % coronary heart disease 55, % osteoarthritis 54, % 9

Whole genome sequencing: 2k ALS, Exceptional age Whole exome

10 Genetic Data generated to date Affymetrix Axiom MVP SNP array 355,000 (late 2016) + 110,000 (April 2018) -> 465,000 Pilots Whole genome sequencing: 2k ALS, Exceptional age Whole exome sequencing: 24K Schizophrenia, Bipolar disorder, African Americans

11 Custom MVP Biobannk Genotyping Array Imputation using 1000 genomes ref. Imputation with HRC is planned

12 Ongoing Scientific Projects with recent renewal submissions Type of Project Topic VA & University Affiliations Alpha test: separate enrollment Schizophrenia and Bipolar Disorder (CSP 572) Alpha test: prototype PTSD in Veterans (CSP 575B) Miami, Bronx, West Haven, & Boston VAs; University of Miami; Mt. Sinai School of Medicine; Yale Univ; Harvard; Stanford San Diego, West Haven, and Boston VAs; UC San Diego; Yale Univ Alpha test: re-contact Gulf War Illness (CSP 2006) East Orange, Durham, West Haven, and Boston VAs; Rutgers, Duke, Yale Beta test Cardiovascular Disease Atlanta & Boston VAs; Emory; Harvard; Boston Univ Beta test Chronic Kidney Disease Nashville & Memphis VAs; Vanderbilt; Univ of Tenn Health Science Center Beta test* Cardio-metabolic Disease Palo Alto, Phila, Albany, Boston, & Phoenix VAs; Univ of Penn; Stanford; Albany Med College; Univ of Mass; Harvard; Arizona State Univ Beta test Multi-substance Abuse Disorders West Haven & Philadelphia VAs; Yale; Univ of Penn Beta test Age-related Macular degeneration Cleveland & Buffalo VAs; Case Western Reserve 12

13 Cardiometabolic Co-PIs: Phil Tsao, Kyong-Mi Chang (Tim Assimes, Scott Damrauer, Julie Lynch) Cardiovascular Co-PIs: Peter Wilson, Kelly Cho (Yan Sun, Chris O Donnell) Palo Alto Albany Bedford Boston Phoenix Philadelphia Atlanta Veterans, ORD, MVP CSP, VINCI, GENISIS 13

Genetic Variation in PCSK9 and PAD Blood Pressure Cardio metabolic Cardiometabolic WG Genetic determinants of T2D

14 Working Groups Lipids WG Genetic analysis of Lipids Genetic Effects of FH Variants on LDL Genetic Effects of FH Variants on CVD Pheno type Lipids CVD Geno type CVD WG CAD: Novel genetic determinants CART: An EHR based GWAS of CAD GWAS for PAD Genetic Variation in PCSK9 and PAD Blood Pressure Cardio metabolic Cardiometabolic WG Genetic determinants of T2D Common/rare variants for BMI Common/rare variants for adult height Metabolic liver disease Blood Pressure WG Genetic Determinants of BP

15 MVP at recent science meetings >50 abstracts AHA Scientific Sessions 2016 AHA Epi Lifestyle 2017 American Society of Human Genetics 2017 AHA Scientific Sessions 2017 American Society of Nephrology (ASN) 2017 American Association for the Study of Liver Diseases (AASLD) 2017 Society for Vascular Surgery Vascular Research Initiatives Conference 2018 other

16 Gamma Projects Genetics of Osteoarthritis Genetics of diabetic complications Genetics of Tinnitus Genetics of Suicidality Predicting Breast Cancer risk in women Veterans Genetics of Gene Expression Rapid electronic phenotyping using APHRODITE 4 more resubmission funded, not yet formally announced

17 Current and Future Genomics Plans Genotype all MVP samples 100,000 whole genome sequences over the next four years Pilot other omics studies Metabolome Methylome Proteome Microbiome Ancillary studies e.g. clinical trials, genotype based recall

18 Ways to collaborate with MVP Must work with investigators of funded projects look up replication for covered phenotypes More customized analysis if working group agrees manuscript proposal --> MPV P&P LOS for grant collaborations that fall under scope of existing projects Cannot accept $$ from outside funding agencies Collaborate with VA based investigator ( 5/8ths) submitting MERIT grant

19 Other Federal Partnerships Collaboration with Department of Energy (DOE) to leverage DOE s exa-scale computing capabilities and VA s big data (CDW and MVP) and genomic expertise to foster big data science, and expand data access Pilot projects: suicide, prostate cancer, CVD risk prediction Collaboration with the National Institutes of Health to enroll Veterans in the All of Us Research Program Collaboration with the Department of Defense to enroll active duty members from Millennium Cohort Study into MVP

20 Summary MVP is a major research initiative to create one of the world s largest databases of genomic, military exposure, lifestyle and health information MVP will lead to better prevention, diagnosis, and treatment of illnesses in Veterans, ultimately, improving health care MVP will allow current Veterans to help transform health care, not only for themselves, but for future generations

When I was young, the service gave me a reason.

Veteran Program so that I can do my part to help future generations of not just Veterans, but everyone

I have always known someone in the family with Diabetes or Hypertension.

21 When I was young, the service gave me a reason. Today, my reason is to help answer those questions yet to be asked I m participating in the Million Veteran Program so that I can do my part to help future generations of not just Veterans, but everyone who can benefit from this research. I have always known someone in the family with Diabetes or Hypertension. I eagerly volunteered to participate in MVP so I can help medical researchers better understand how genes influence diseases. One blood draw is all it took yet the potential to contribute to scientific discoveries is enormous! I believe that the data collected from me and other Veterans in the Million Veterans Program will someday provide better ways to diagnose and treat patients. I volunteered to participate in the MVP because I want to do my part to make this a reality one day.

Big Data Phenomics in the VA. Outline

Big Data Phenomics in the VA. Outline Big Phenomics in the VA Mary Whooley MD Director, VA Measurement Science QUERI San Francisco VA Health Care System University of California, San Francisco Kelly Cho PhD MPH Phenomics Lead, Million Veteran