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Polygenic risk scores: pleiotropy and the effect of environment.

Publication ,  Journal Article
Loika, Y; Irincheeva, I; Culminskaya, I; Nazarian, A; Kulminski, AM
Published in: GeroScience
December 2020

Polygenic risk scores (PRSs) discriminate trait risks better than single genetic markers because they aggregate the effects of risk alleles from multiple genetic loci. Constructing pleiotropic PRSs and understanding heterogeneity, and the replication of PRS-trait associations can strengthen its applications. By using variational Bayesian multivariate high-dimensional regression, we constructed pleiotropic PRSs jointly associated with body mass index, systolic and diastolic blood pressure, total and high-density lipoprotein cholesterol in a sample of 18,108 Caucasians from three independent cohorts. We found that dissecting heterogeneity associated with birth year, which is a proxy of exogenous exposures, improved the replication of significant PRS-trait associations from 37.5% (6 of 16) in the entire sample to 90% (18 of 20) in the more homogeneous sample of individuals born before the year 1925. Our findings suggest that secular changes in exogenous exposures may substantially modify pleiotropic risk profiles affecting translation of genetic discoveries into health care.

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Published In

GeroScience

DOI

EISSN

2509-2723

ISSN

2509-2715

Publication Date

December 2020

Volume

42

Issue

6

Start / End Page

1635 / 1647

Related Subject Headings

  • Risk Factors
  • Phenotype
  • Humans
  • Blood Pressure
  • Bayes Theorem
  • Alleles
  • 3202 Clinical sciences
  • 3105 Genetics
 

Citation

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Chicago
ICMJE
MLA
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Loika, Y., Irincheeva, I., Culminskaya, I., Nazarian, A., & Kulminski, A. M. (2020). Polygenic risk scores: pleiotropy and the effect of environment. GeroScience, 42(6), 1635–1647. https://doi.org/10.1007/s11357-020-00203-2
Loika, Yury, Irina Irincheeva, Irina Culminskaya, Alireza Nazarian, and Alexander M. Kulminski. “Polygenic risk scores: pleiotropy and the effect of environment.GeroScience 42, no. 6 (December 2020): 1635–47. https://doi.org/10.1007/s11357-020-00203-2.
Loika Y, Irincheeva I, Culminskaya I, Nazarian A, Kulminski AM. Polygenic risk scores: pleiotropy and the effect of environment. GeroScience. 2020 Dec;42(6):1635–47.
Loika, Yury, et al. “Polygenic risk scores: pleiotropy and the effect of environment.GeroScience, vol. 42, no. 6, Dec. 2020, pp. 1635–47. Epmc, doi:10.1007/s11357-020-00203-2.
Loika Y, Irincheeva I, Culminskaya I, Nazarian A, Kulminski AM. Polygenic risk scores: pleiotropy and the effect of environment. GeroScience. 2020 Dec;42(6):1635–1647.

Published In

GeroScience

DOI

EISSN

2509-2723

ISSN

2509-2715

Publication Date

December 2020

Volume

42

Issue

6

Start / End Page

1635 / 1647

Related Subject Headings

  • Risk Factors
  • Phenotype
  • Humans
  • Blood Pressure
  • Bayes Theorem
  • Alleles
  • 3202 Clinical sciences
  • 3105 Genetics