Using Population
Descriptors in Genetics
and Genomics Research

A New Framework for an Evolving Field

______

Committee on the Use of Race, Ethnicity, and Ancestry
as Population Descriptors in Genomics Research

Board on Health Sciences Policy

Health and Medicine Division

Committee on Population

Division of Behavioral and Social Sciences and Education

Consensus Study Report

NATIONAL ACADEMIES PRESS 500 Fifth Street, NW, Washington, DC 20001

This project has been funded with federal funds under Contract No. HHSN263201800029I (75N98021F00009) between the National Academy of Sciences and the Department of Health and Human Services, National Institutes of Health: All of Us Research Program; National Cancer Institute; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Environmental Health Sciences; National Institute of Nursing Research; National Institute on Aging; National Institute on Drug Abuse; National Institute on Minority Health and Health Disparities; NIH Office of Behavioral and Social Sciences Research; and NIH Office of Science Policy. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-70065-8
International Standard Book Number-10: 0-309-70065-5
Digital Object Identifier: https://doi.org/10.17226/26902

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. Using population descriptors in genetics and genomics research: A new framework for an evolving field. Washington, DC: The National Academies Press. https://doi.org/10.17226/26902.

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COMMITTEE ON THE USE OF RACE, ETHNICITY, AND ANCESTRY AS POPULATION DESCRIPTORS IN GENOMICS RESEARCH¹

ARAVINDA CHAKRAVARTI (Cochair), Director, Center for Human Genetics and Genomics; Muriel G. & George W. Singer Professor of Neuroscience and Physiology, Professor of Medicine, New York University Grossman School of Medicine

CHARMAINE ROYAL (Cochair), Robert O. Keohane Professor of African & African American Studies, Biology, Global Health, and Family Medicine & Community Health; Director, Center on Genomics, Race, Identity, Difference and Center for Truth, Racial Healing & Transformation, Duke University

KATRINA ARMSTRONG, Executive Vice President, Health and Biomedical Sciences; Dean of the Vagelos College of Physicians and Surgeons and the Faculties of Health Sciences; Harold and Margaret Hatch Professor of the University; Columbia University

MICHAEL BAMSHAD, Professor and Chief, Division of Genetic Medicine, Department of Pediatrics; Allan and Phyllis Treuer Endowed Chair, Genetics and Development, University of Washington and Seattle Children’s Hospital

LUISA N. BORRELL, Distinguished Professor, Department of Epidemiology & Biostatistics, Graduate School of Public Health & Health Policy, City University of New York

KATRINA CLAW, Assistant Professor, Department of Biomedical Informatics, School of Medicine; Faculty, Colorado Center for Personalized Medicine, University of Colorado Denver–Anschutz Medical Campus

CLARENCE C. GRAVLEE, Associate Professor, Department of Anthropology, University of Florida

MARK D. HAYWARD, Professor of Sociology; Centennial Commission Professor in Liberal Arts; Faculty Research Associate, Population Research Center, University of Texas at Austin

RICK KITTLES, Senior Vice President for Research; Professor of Community Health and Preventive Medicine, Morehouse School of Medicine

SANDRA SOO-JIN LEE, Professor of Medical Humanities & Ethics; Chief of the Division of Ethics, Department of Medical Humanities & Ethics, Vagelos College of Physicians & Surgeons, Columbia University

___________________

¹ See Appendix F, Disclosure of Unavoidable Conflict of Interest.

ANDRÉS MORENO-ESTRADA, Professor, Advanced Genomics Unit, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico

ANN MORNING, James Weldon Johnson Professor of Sociology, New York University

JOHN P. NOVEMBRE, Professor, Department of Human Genetics, Department of Ecology & Evolution, University of Chicago

MOLLY PRZEWORSKI, Professor, Department of Biological Sciences, Department of Systems Biology, Columbia University

DOROTHY E. ROBERTS, George A. Weiss University Professor of Law & Sociology; Raymond Pace & Sadie Tanner Mossell Alexander Professor of Civil Rights; Professor of Africana Studies; Director, Penn Program on Race, Science & Society, University of Pennsylvania

SARAH A. TISHKOFF, David and Lyn Silfen University Professor, Departments of Genetics and Biology; Director, Center for Global Genomics & Health Equity, University of Pennsylvania

GENEVIEVE L. WOJCIK, Assistant Professor of Epidemiology, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health

Study Staff

SARAH H. BEACHY, Study Director

SAMANTHA N. SCHUMM, Associate Program Officer

LEAH CAIRNS, Study Codirector (until October 2022)

KATHRYN ASALONE, Associate Program Officer

MEREDITH HACKMANN, Associate Program Officer

LYDIA TEFERRA, Research Assistant

APARNA CHERAN, Senior Program Assistant (from June 2022)

MICHAEL K. ZIERLER, Science Writer

ANDREW M. POPE, Senior Director, Board on Health and Sciences Policy (until July 2022)

CLARE STROUD, Senior Director, Board on Health and Sciences Policy (from July 2022)

MALAY K. MAJMUNDAR, Director, Committee on Population

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by SUSAN J. CURRY of the University of Iowa and LINDA C. DEGUTIS of the Yale School of Public Health. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The study committee and project staff acknowledge that the National Academies of Sciences, Engineering, and Medicine is physically housed on the traditional land of the Nacotchtank (Anacostan) and Piscataway Peoples, past and present. The committee and staff honor with gratitude the land itself and the people who have stewarded it throughout the generations. They honor and respect the enduring relationship that exists between these peoples and nations and this land. The committee and staff thank these peoples for their resilience in protecting this land and aspire to uphold our responsibilities to their example. The committee and staff also acknowledge the countless number of people who have participated, both willingly and unwillingly, in biomedical research, as well as those who have raised the issues addressed in this study for many years.

The study committee and project staff would like to thank the study sponsor—the 14 institutes, program, and offices of the National Institutes of Health—for their leadership on this issue and for their vision and commitment to developing and supporting this project. The committee and staff express their gratitude to the many experts who shared their diverse perspectives and advice with the committee throughout the process and during the public sessions. The committee is grateful for the staff within the Health and Medicine Division who provided support and guidance for the project, along with their collaborators in the Division of Behavioral and Social Sciences and Education.

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Contents

LIST OF BOXES, FIGURES, AND TABLES

PREFACE

ABBREVIATIONS

SUMMARY

SECTION I: PAST AND CURRENT USE OF POPULATION DESCRIPTORS IN GENETICS AND GENOMICS RESEARCH

Section I Overview

1 POPULATION DESCRIPTORS IN HUMAN GENETICS RESEARCH: GENESIS, EVOLUTION, AND CHALLENGES

The Study of Human Genetic Variation

What Is a Study Using Genetic Information Trying to Accomplish?

Classification of Genomics Study Types

Features of Human Genome Variation

Population Classification Schemes in Genetics and Genomics Research

Attempts to Address the Use of Race, Ethnicity, and Ancestry in the Genomic Era

Why Is This Study Important? Why Another Study? Why Now?

What Is the Goal of This Report?

References

2 A MULTIPLICITY OF DESCRIPTORS IN GENETICS AND GENOMICS RESEARCH

Introduction

A Range of Descent-Associated Population Descriptors

The Importance of Environmental Factors in Genetics and Genomics Research

References

SECTION II: RECOMMENDATIONS

Section II Overview

3 GUIDING PRINCIPLES

Introduction

Principles

Synergy Among and Tension Between Guiding Principles

References

4 REQUISITES FOR SUSTAINED CHANGE

Introduction

Typological Thinking

Environmental Factors

Community Engagement

References

5 GUIDANCE FOR SELECTION AND USE OF POPULATION DESCRIPTORS IN GENOMICS RESEARCH

Introduction

The Importance of Transparency and Specificity When Selecting and Reporting Population Descriptors

Conclusion and Recommendations

Tools for Selecting and Using Population Descriptors in Genetics and Genomics Research

Considerations for Harmonization of Population Descriptors Across Studies

References

6 IMPLEMENTATION AND ACCOUNTABILITY

Introduction

Implementation Across the Genomics Research Ecosystem

Recommendations

Mechanisms of Accountability

Parting Thoughts

References

APPENDIXES

A STUDY APPROACH AND METHODS

B GLOSSARY

C TABLE OF INTERNATIONAL PROGRAMS

D DECISION TREE FOR THE USE OF POPULATION DESCRIPTORS IN GENOMICS RESEARCH

E COMMITTEE AND STAFF BIOSKETCHES

F DISCLOSURE OF UNAVOIDABLE CONFLICT OF INTEREST

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List of Boxes, Figures, and Tables

BOXES

S-1 Key Terminology and Definitions

1-1 Race, Science, and Society: A Reference List

1-2 Statement of Task

2-1 Key Terminology and Definitions

5-1 Key Terminology for This Chapter

5-2 Common Data Elements for Researchers to Include as Metadata to Help Harmonize Across Studies

5-3 Concise Language for Genetic Similarity: The Abbreviation + -Like System

6-1 Example Checklist that Funders of Genetics and Genomics Research Can Implement for Researchers

6-2 Example Checklist that Journals Can Implement for Genomics Researchers

FIGURES

S-1 A framework for change

2-1 Visualization of genealogical vs. genetic ancestry

2-2 U.S. Census race and ethnicity categories over time (1790–2020)

II-1 A framework for change

D-1 Decision tree for the use of population descriptors in genomics research

TABLES

S-1 Recommended Approaches for the Use of Population Descriptors by Genomics Study Type

1-1 Comparison of Classification Schemes Used in Three Studies Using Genetics from Three Distinct Global Contexts

5-1 Recommended Approaches for the Use of Population Descriptors by Genomics Study Type

A-1 Literature Search Terms

C-1 International Programs

Preface

Human genetics studies that assess the contributions of genes to phenotypes can be conducted either using relatives or groups of distantly related individuals (“unrelated” in a colloquial sense). In both instances, geneticists search for a pattern of genetic (sequence or allelic) variation that can distinguish between different forms of a phenotype, say, individuals with sickle cell anemia from those with sickle cell trait, based on the known rules of Mendelian genetic transmission. Although the expected similarity or dissimilarity of closely related individuals largely depends on gene transmission rules, that between more distantly related individuals mostly depends on their remote ancestral histories, such as where, when, and how their common ancestors arose. This information is partially captured by affiliation of an individual to a population; however, how a population should be defined for any specific question in genetics research is less clear. Nevertheless, for any human genetics research, now extended to entire genomes, it is critical to clearly describe who is selected for a study, why, and how. Researchers also need to specify the criteria used to describe participants, including the use of population descriptors. Unfortunately, genetics studies have not named individuals consistently or in a principled manner, often reflexively using race and ethnicity without great thought or justification. Though seldom studied, measures of the environments associated with study individuals and groups are also germane to our understanding of genetic traits and disorders and need to be included.

In recent years, genetic information has become far more accessible. The number of human genetics and genomics studies is rapidly increasing, and many such studies are led by investigators who were not primarily

trained in human genetics. While this study focuses mainly on knowledge from human genetics and genomics, we acknowledge that knowledge from many other sources (oral, archaeological, traditional, community, etc.) serves to inform our identities, history, relationships to other humans, and our traits and diseases. It is time for us to reshape how genetics studies are conceptualized, conducted, and interpreted.

This commissioned study describes an effort to clarify the scientific rationales for describing research participants and their group labels. We start with a historical view of how we got to our current state, then proceed to examine how else we could achieve our scientific aims, and follow with our recommendations and suggested implementations to improve genetic and genomic science. Our overarching goal is to motivate researchers to consider when population descriptors are necessary, which ones are appropriate for a specific type of genetics study design, whether multiple descriptors are necessary, and what additional information is needed for genetic dissection of phenotypes. Accordingly, this report is divided into two sections; the first is “Past and Current Use of Population Descriptors,” and the second section is “Recommendations.”

Aravinda Chakravarti and Charmaine Royal,
Cochairs, Committee on the Use of Race, Ethnicity, and
Ancestry as Population Descriptors in Genomics Research

Abbreviations

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