The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations

Laura M Amendola¹, Jonathan S Berg², Carol R Horowitz³, Frank Angelo¹, Jeannette T Bensen⁴, Barbara B Biesecker⁵, Leslie G Biesecker⁶, Gregory M Cooper⁷, Kelly East⁷, Kelly Filipski⁸, Stephanie M Fullerton⁹, Bruce D Gelb¹⁰, Katrina A B Goddard¹¹, Benyam Hailu¹², Ragan Hart¹, Kristen Hassmiller-Lich¹³, Galen Joseph¹⁴, Eimear E Kenny¹⁵, Barbara A Koenig¹⁶, Sara Knight¹⁷, Pui-Yan Kwok¹⁸, Katie L Lewis⁶, Amy L McGuire¹⁹, Mary E Norton²⁰, Jeffrey Ou¹, Donald W Parsons²¹, Bradford C Powell², Neil Risch¹⁸, Mimsie Robinson²², Christine Rini²³, Sarah Scollon²⁴, Anne M Slavotinek²⁵, David L Veenstra²⁶, Melissa P Wasserstein²⁷, Benjamin S Wilfond²⁸, Lucia A Hindorff²⁹; CSER consortium; Sharon E Plon²⁴, Gail P Jarvik³⁰

Affiliations

¹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
² Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Center for Health Equity and Community Engaged Research, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Research Triangle Institute, International, Washington DC 20005, USA.
⁶ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷ HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
⁸ National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA.
⁹ Department of Bioethics and Humanities, University of Washington, Seattle, WA 98195, USA.
¹⁰ Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹¹ Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227, USA.
¹² National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892, USA.
¹³ Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁴ Department of Anthropology, History & Social Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
¹⁵ Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁶ Program in Bioethics, Institute for Health and Aging, University of California-San Francisco, San Francisco, CA 94118, USA.
¹⁷ Division of Preventive Medicine, University of Alabama at Birmingham, and Birmingham VA Medical Center, Birmingham, AL 35294, USA.
¹⁸ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁹ Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX 77030, USA.
²⁰ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
²¹ Texas Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
²² Bethel Gospel Assembly, New York, NY 10035, USA.
²³ Department of Biomedical Research, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USA.
²⁴ Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
²⁵ Department of Pediatrics, Division of Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
²⁶ Department of Pharmacy, University of Washington, Seattle, WA 98195, USA.
²⁷ Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
²⁸ Department of Pediatrics and Seattle Children's Research Institute, University of Washington, Seattle, WA 98195, USA.
²⁹ Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
³⁰ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: gjarvik@medicine.washington.edu.

PMID: 30193136
PMCID: PMC6128306
DOI: 10.1016/j.ajhg.2018.08.007

The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations

Laura M Amendola et al. Am J Hum Genet. 2018.

. 2018 Sep 6;103(3):319-327.

doi: 10.1016/j.ajhg.2018.08.007.

Authors

Affiliations

¹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
² Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Center for Health Equity and Community Engaged Research, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Research Triangle Institute, International, Washington DC 20005, USA.
⁶ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷ HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
⁸ National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA.
⁹ Department of Bioethics and Humanities, University of Washington, Seattle, WA 98195, USA.
¹⁰ Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹¹ Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227, USA.
¹² National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892, USA.
¹³ Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁴ Department of Anthropology, History & Social Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
¹⁵ Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁶ Program in Bioethics, Institute for Health and Aging, University of California-San Francisco, San Francisco, CA 94118, USA.
¹⁷ Division of Preventive Medicine, University of Alabama at Birmingham, and Birmingham VA Medical Center, Birmingham, AL 35294, USA.
¹⁸ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁹ Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX 77030, USA.
²⁰ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
²¹ Texas Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
²² Bethel Gospel Assembly, New York, NY 10035, USA.
²³ Department of Biomedical Research, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USA.
²⁴ Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
²⁵ Department of Pediatrics, Division of Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
²⁶ Department of Pharmacy, University of Washington, Seattle, WA 98195, USA.
²⁷ Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
²⁸ Department of Pediatrics and Seattle Children's Research Institute, University of Washington, Seattle, WA 98195, USA.
²⁹ Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
³⁰ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: gjarvik@medicine.washington.edu.

PMID: 30193136
PMCID: PMC6128306
DOI: 10.1016/j.ajhg.2018.08.007

Abstract

The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in its second funding cycle, is investigating the effectiveness of integrating genomic (exome or genome) sequencing into the clinical care of diverse and medically underserved individuals in a variety of healthcare settings and disease states. The consortium comprises a coordinating center, six funded extramural clinical projects, and an ongoing National Human Genome Research Institute (NHGRI) intramural project. Collectively, these projects aim to enroll and sequence over 6,100 participants in four years. At least 60% of participants will be of non-European ancestry or from underserved settings, with the goal of diversifying the populations that are providing an evidence base for genomic medicine. Five of the six clinical projects are enrolling pediatric patients with various phenotypes. One of these five projects is also enrolling couples whose fetus has a structural anomaly, and the sixth project is enrolling adults at risk for hereditary cancer. The ongoing NHGRI intramural project has enrolled primarily healthy adults. Goals of the consortium include assessing the clinical utility of genomic sequencing, exploring medical follow up and cascade testing of relatives, and evaluating patient-provider-laboratory level interactions that influence the use of this technology. The findings from the CSER consortium will offer patients, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of providing genomic medicine in diverse populations and settings, and contribute evidence toward developing best practices for the delivery of clinically useful and cost-effective genomic sequencing in diverse healthcare settings.

PubMed Disclaimer

Figures

**Figure 1**
Structure of the CSER Consortium The components of the CSER consortium and their relationships to each other.

See this image and copyright information in PMC

References

1. Green R.C., Goddard K.A.B., Jarvik G.P., Amendola L.M., Appelbaum P.S., Berg J.S., Bernhardt B.A., Biesecker L.G., Biswas S., Blout C.L., CSER Consortium Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. Am. J. Hum. Genet. 2016;98:1051–1066. - PMC - PubMed
1. Yavarna T., Al-Dewik N., Al-Mureikhi M., Ali R., Al-Mesaifri F., Mahmoud L., Shahbeck N., Lakhani S., AlMulla M., Nawaz Z. High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders. Hum. Genet. 2015;134:967–980. - PubMed
1. Lee K., Berg J.S., Milko L., Crooks K., Lu M., Bizon C., Owen P., Wilhelmsen K.C., Weck K.E., Evans J.P., Garg S. High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting. Am. J. Ophthalmol. 2015;160:354–363.e9. - PMC - PubMed
1. Yang Y., Muzny D.M., Xia F., Niu Z., Person R., Ding Y., Ward P., Braxton A., Wang M., Buhay C. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014;312:1870–1879. - PMC - PubMed
1. Amendola L.M., Dorschner M.O., Robertson P.D., Salama J.S., Hart R., Shirts B.H., Murray M.L., Tokita M.J., Gallego C.J., Kim D.S. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015;25:305–315. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations

Affiliations

The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources