Heritability, pQTLs, and environmental influence on proteins involved in age, cardiovascular risk, and glucose tolerance using the SomaScan® Assay

Background

  • Cis-pQTLs: genetic variants correlated with levels of nearby proteins
  • Cis-pQTLs are one piece of evidence of specificity for affinity-based proteomic assays; also useful for proteogenomic analyses, such as Mendelian randomization
  • Protein levels reflect genetics, environment, and physiology, so not all proteins will have strong genetic
    associations
  • Non-genetic influences captured by the proteome contribute to phenotypic variation

Methods

  • Compiled a list of cis-pQTLs from 15 studies run on the SomaScan Assay [1-15], and extracted aptamer heritability from published results [14].
  • Cross-tabulated cis-pQTL association and strong endpoint association (FDR < 10%): age, four-year cardiovascular disease risk (CVD), and oral glucose tolerance tests [16-17].

SomaScan® Assay Technology

  • Measures 11,000 proteins using modified aptamers
  • 10-log dynamic range
  • Standardization method that enables easy cross-study data integration
  • 21 SomaSignal® tests for non-invasive risk assessment and physiological measurements
  • Ecosystem of publications and data analysis tools

Conclusions

  • Endpoint-associated analytes are more likely to have a cis-pQTL or have non-zero heritability than non-endpoint-associated analytes
  • Most analytes are sensitive to environmental effects
    • Many endpoint-associated analytes do not have evidence of genetic influence
    • Heritability levels are generally modest
  • The variation in protein levels detected by the SomaScan Assay is reflective of both genetic variation and of non-genetic variation

Authors

Brendan Epstein
Ted Johnson
Tina Lai
Michael A. Hinterberg
David P. Astling

SomaLogic Operating Co., Inc., Boulder, CO USA


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