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Summarizing polygenic risks for complex diseases in a clinical whole-genome report.

Publication ,  Journal Article
Kong, SW; Lee, I-H; Leshchiner, I; Krier, J; Kraft, P; Rehm, HL; Green, RC; Kohane, IS; MacRae, CA; MedSeq Project,
Published in: Genetics in medicine : official journal of the American College of Medical Genetics
July 2015

Disease-causing mutations and pharmacogenomic variants are of primary interest for clinical whole-genome sequencing. However, estimating genetic liability for common complex diseases using established risk alleles might one day prove clinically useful.We compared polygenic scoring methods using a case-control data set with independently discovered risk alleles in the MedSeq Project. For eight traits of clinical relevance in both the primary-care and cardiomyopathy study cohorts, we estimated multiplicative polygenic risk scores using 161 published risk alleles and then normalized them using the population median estimated from the 1000 Genomes Project.Our polygenic score approach identified the overrepresentation of independently discovered risk alleles in cases as compared with controls using a large-scale genome-wide association study data set. In addition to normalized multiplicative polygenic risk scores and rank in a population, the disease prevalence and proportion of heritability explained by known common risk variants provide important context in the interpretation of modern multilocus disease risk models.Our approach in the MedSeq Project demonstrates how complex trait risk variants from an individual genome can be summarized and reported for the general clinician and also highlights the need for definitive clinical studies to obtain reference data for such estimates and to establish clinical utility.

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Published In

Genetics in medicine : official journal of the American College of Medical Genetics

DOI

EISSN

1530-0366

ISSN

1098-3600

Publication Date

July 2015

Volume

17

Issue

7

Start / End Page

536 / 544

Related Subject Headings

  • Reproducibility of Results
  • Multifactorial Inheritance
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Genetics & Heredity
  • Genetic Testing
  • Genetic Predisposition to Disease
  • Genetic Association Studies
  • Case-Control Studies
 

Citation

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Kong, S. W., Lee, I.-H., Leshchiner, I., Krier, J., Kraft, P., Rehm, H. L., … MedSeq Project, . (2015). Summarizing polygenic risks for complex diseases in a clinical whole-genome report. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 17(7), 536–544. https://doi.org/10.1038/gim.2014.143
Kong, Sek Won, In-Hee Lee, Ignaty Leshchiner, Joel Krier, Peter Kraft, Heidi L. Rehm, Robert C. Green, Isaac S. Kohane, Calum A. MacRae, and Calum A. MedSeq Project. “Summarizing polygenic risks for complex diseases in a clinical whole-genome report.Genetics in Medicine : Official Journal of the American College of Medical Genetics 17, no. 7 (July 2015): 536–44. https://doi.org/10.1038/gim.2014.143.
Kong SW, Lee I-H, Leshchiner I, Krier J, Kraft P, Rehm HL, et al. Summarizing polygenic risks for complex diseases in a clinical whole-genome report. Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Jul;17(7):536–44.
Kong, Sek Won, et al. “Summarizing polygenic risks for complex diseases in a clinical whole-genome report.Genetics in Medicine : Official Journal of the American College of Medical Genetics, vol. 17, no. 7, July 2015, pp. 536–44. Epmc, doi:10.1038/gim.2014.143.
Kong SW, Lee I-H, Leshchiner I, Krier J, Kraft P, Rehm HL, Green RC, Kohane IS, MacRae CA, MedSeq Project. Summarizing polygenic risks for complex diseases in a clinical whole-genome report. Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Jul;17(7):536–544.

Published In

Genetics in medicine : official journal of the American College of Medical Genetics

DOI

EISSN

1530-0366

ISSN

1098-3600

Publication Date

July 2015

Volume

17

Issue

7

Start / End Page

536 / 544

Related Subject Headings

  • Reproducibility of Results
  • Multifactorial Inheritance
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Genetics & Heredity
  • Genetic Testing
  • Genetic Predisposition to Disease
  • Genetic Association Studies
  • Case-Control Studies