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The PhenX Project: Consensus Measures for Phenotypes & Exposures

Erin M. Ramos, PhD MPH

Division of Genomic Medicine

NHGRI

9/8/15: NIH CDE Initiatives – Overview Webinar

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Standard Measures Needed – c2006

Combining studies increases ability to detect loci with moderate effect size (G x G; G x E interactions)

Replication of GWAS results

Potential for cross-study analysis and replication limited by lack of standardized measures

(www.broad.mit.edu/diabetes/scandinavs/type2.html)

Type 2 Diabetes GWAS (>380K SNPs)

The PhenX Project

• Goal: Produce an online resource of standard phenotypic & environmental exposure measures

• Cooperative Agreement (2007 U01 2013 U41)

• ~ 450 measures addressing 21 domains

• Protocols, data element dictionaries, data collections worksheets (www.phenxtoolkit.org)

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PhenX Definitions DOMAIN: Topical area with unifying

theme (organ system, complex disease)

Substance Use

MEASURE: Certain characteristic of, or relating to, a study subject Nicotine Dependence

PROTOCOL: Standard procedure recommended collecting and record a PhenX measure

Fagerstrom Test

COLLECTION: A set of measures with a shared characteristic, target population or topic. The measures may cut across research Domains.

Mental Health Research 4

Steering Committee

Steering Committee

NHGRINHGRI RTIRTI

NIH IC LiaisonsNIH IC

Liaisons

External Scientific

Panel

External Scientific

Panel

Cardiovascular DiabetesDemographics

CancerAnthropometrics

Environmental Exposures

Nutrition/Dietary SupplementsGastrointestinal NeurologyInfectious Disease

& Immunity

Ocular PsychosocialOral Health PsychiatricPhysical Activity & Fitness

Reproductive Health

Speech and HearingRespiratory Social

EnvironmentsSkin, Bone,

Muscle & Joint

Alcohol, Tobacco, Other Substances

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Rare Genetic Conditions

Obesity

Pregnancy and Pediatrics

TBD

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Selecting PhenX Measures

Criteria for selecting measures include: - Well-established and broadly

validated

- Low burden to participant & investigator

- Applicable across population groups

- Freely available protocols

- Useful to investigators who are not domain experts

WG refines scopeWG refines scope

SC defines scopeSC defines scope

WG selects prelim measures

WG selects prelim measures

Community Outreach

Community Outreach

WG selects final measures

WG selects final measures

Searching the Toolkit

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My Toolkit

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NIH Collaborations

PhenX Domains

(N=25)

9Kevin Conway

Greg Farber

Kay Wanke

Ellen Werner

PhenX CDEs and variables

21 Domains (demographics, diabetes, etc.)- 389 CDEs (CDEs are created for each protocol)- 11,961 variables

Substance Abuse and Addiction Collections- 121 CDEs- 3,009 variables

Mental Health Research Collections- 39 CDEs to date- 893 variables

Tobacco Regulatory Research Collections- 21 CDEs to date- 200 variables

10(Slide provided by C. Hamilton, PhenX PI)

Example of PhenX CDEs and Variables

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Protocol Name Protocol CDE NameProtocol CDE ID VARNAME

Birthplace of Grandparents

Maternal Grandmother Geographic Birth Place Text 2789935 PX010401_Maternal_Grandmother_Bi

rthplaceBirthplace of Grandparents

Maternal Grandmother Geographic Birth Place Text 2789935 PX010401_Maternal_Grandmother_Bi

rthplace_LocationBirthplace of Grandparents

Maternal Grandfather Geographic Birth Place Text 2789937

PX010401_Maternal_Grandfather_Birthplace

Birthplace of Grandparents

Maternal Grandfather Geographic Birth Place Text 2789937

PX010401_Maternal_Grandfather_Birthplace_Location

Birthplace of Grandparents

Paternal Grandmother Geographic Birth Place Text 2789939 PX010401_Paternal_Grandmother_Bir

thplaceBirthplace of Grandparents

Paternal Grandmother Geographic Birth Place Text 2789939 PX010401_Paternal_Grandmother_Bir

thplace_LocationBirthplace of Grandparents

Paternal Grandfather Geographic Birth Place Text 2789941 PX010401_Paternal_Grandfather_Birt

hplaceBirthplace of Grandparents

Paternal Grandfather Geographic Birth Place Text 2789941 PX010401_Paternal_Grandfather_Birt

hplace_Location

1 Protocol, 4 CDEs, 8 variables

(Slide provided by C. Hamilton, PhenX PI)

Linking to relevant efforts

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Adding Value by Crowdsourcing

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Closing thoughts

Lessons learned- Identifying NIH IC Liaisons early was important- Personalized emails are most effective for outreach- Evaluating update/adoption of PhenX is not easy

2,000 Registered Users, 97 FOAs

- Science changes, re-evaluate content often (PhenX Expert Review Panels) and have strong versioning system

Looking ahead- Protocol translations, education & outreach- dbGaP mapping, EHR integration, participate in trans-NIH

CDE efforts

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Acknowledgments

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NHGRI - Brenda Iglesias (Program

Analyst) PhenX Steering Committee

- Mary Marazita, Co-Chair- Cathy McCarty, Co-Chair- Sharon Terry, Member

WG Chairs / Members NIH Liaisons Other Liaisons: HHS, DoD, CDC,

FDA, VA NIDA lead – Kevin Conway TRSP lead – Kay Wanke NIMH lead – Greg Farber NHLBI lead – Ellen Werner

RTI Team- Carol Hamilton (Principal

Investigator)- Tabitha Hendershot (Co-

Investigator)- Amanda Riley (Project

Manager)- Darigg Brown- Wayne Huggins- Debbie Maiese- Destiney Nettles- Helen Pan- Mike Phillips- Toolkit team- Communications team- Logistics team

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Contact Information

Erin M. Ramos, PhD MPH Program Director, Division of Genomic Medicine

National Human Genome Research Institute

5635 Fishers Lane, Suite 4076, MSC 9305

Bethesda, MD 20892-9305

Tel: 301.451.3706  

RAMOSER@MAIL.NIH.GOV

Appendix

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Toolkit Stats (July 2015)

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• Number of Registered Users: 1,949• Number of Countries that Accessed PhenX : 155• Number of Visits: 713,446• Number of Unique Visits: 118,695• Average Visits Per Day: 301• Report Downloads: 4,830• Register Your Study: 16• Publications Citing PhenX: 94• Number of Funding Opportunities: 97

PhenX at ASHG Annual Meeting 2015

ASHG Invited Sessions on October 7, 2015 “Human Phenotypes for Researchers, Clinicians,

and Patients” Moderator: Jonathan Haines Speakers: C. McCarty, A. Kho, H. Rehm, B.

Patrick-Lake

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Add Value by PhenX/dbGaP Mapping

Huge # of variables in dbGaP (160,188) Fewer # of variables in PhenX (16,112) Mapping Comparable Variables Only

PhenX var => dbGAP var (harmonizable) same concept dbGAP var => PhenX var (harmonizable) same concept

Tools- In-house web-based wrapper using NCBI search API- Drill down using dbGaP search pages

Evaluating effectiveness of two mapping procedures Establish a schedule based on results

20(Slide provided by C. Hamilton, PhenX PI)

PhenX Phase II Improve Toolkit Content

- 4 new domains- Review/Update PhenX domains

Extend Capabilities- Chinese and Spanish translations- Web-based protocols, Explore EHR Integration

Mapping PhenX Measures to studies in dbGaP- Identify opportunities to combine studies

Collaborations and Outreach

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“A complete understanding of disease also requires…high-quality phenotypic data. Obtaining phenotypic data that are both thorough and accurate enough to be analyzed in conjunction with genomic and environ mental data requires meticulous application of phenotyping methods, improved definitions of phenotypes, new technologies, and the consist ent use of data standards (http://www.phenx.org).”

Green and Guyer, 2011