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Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach.

Publication ,  Journal Article
Goldstein, BA; Yang, L; Salfati, E; Assimes, TL
Published in: Genet Epidemiol
September 2015

Genetic risk scores are an increasingly popular tool for summarizing the cumulative risk of a set of Single Nucleotide Polymorphisms (SNPs) with disease. Typically only the set of the SNPs that have reached genome-wide significance compose these scores. However recent work suggests that including additional SNPs may aid risk assessment. In this paper, we used the Atherosclerosis Risk in Communities (ARIC) Study cohort to illustrate how one can choose the optimal set of SNPs for a genetic risk score (GRS). In addition to P-value threshold, we also examined linkage disequilibrium, imputation quality, and imputation type. We provide a variety of evaluation metrics. Results suggest that P-value threshold had the greatest impact on GRS quality for the outcome of coronary heart disease, with an optimal threshold around 0.001. However, GRSs are relatively robust to both linkage disequilibrium and imputation quality. We also show that the optimal GRS partially depends on the evaluation metric and consequently the way one intends to use the GRS. Overall the implications highlight both the robustness of GRS and a means to empirically choose the best set of GRSs.

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Published In

Genet Epidemiol

DOI

EISSN

1098-2272

Publication Date

September 2015

Volume

39

Issue

6

Start / End Page

439 / 445

Location

United States

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Female
  • Epidemiology
 

Citation

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Goldstein, B. A., Yang, L., Salfati, E., & Assimes, T. L. (2015). Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach. Genet Epidemiol, 39(6), 439–445. https://doi.org/10.1002/gepi.21912
Goldstein, Benjamin A., Lingyao Yang, Elias Salfati, and Themistoclies L. Assimes. “Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach.Genet Epidemiol 39, no. 6 (September 2015): 439–45. https://doi.org/10.1002/gepi.21912.
Goldstein BA, Yang L, Salfati E, Assimes TL. Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach. Genet Epidemiol. 2015 Sep;39(6):439–45.
Goldstein, Benjamin A., et al. “Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach.Genet Epidemiol, vol. 39, no. 6, Sept. 2015, pp. 439–45. Pubmed, doi:10.1002/gepi.21912.
Goldstein BA, Yang L, Salfati E, Assimes TL. Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach. Genet Epidemiol. 2015 Sep;39(6):439–445.
Journal cover image

Published In

Genet Epidemiol

DOI

EISSN

1098-2272

Publication Date

September 2015

Volume

39

Issue

6

Start / End Page

439 / 445

Location

United States

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Female
  • Epidemiology