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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