Heritability, pQTLs, and environmental influence on proteins involved in age, cardiovascular risk, and glucose tolerance using the SomaScan® Assay
- 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
- Non-genetic influences captured by the proteome contribute to phenotypic variation
- Compiled a list of cis-pQTLs from 15 studies run on the SomaScan Assay [1-15], and extracted aptamer heritability from published results .
- 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
- 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
Michael A. Hinterberg
David P. Astling
SomaLogic Operating Co., Inc., Boulder, CO USA
PosterComparison of Proteomic CV Risk to Established ASCVD 10-Year Risk Decision Points
The ASCVD pooled cohort equation (PCE) is well-established for CV risk assessment. Decision points for determining treatment plans are low, intermediate and high risk over 10 years, however this approach over and underestimates risk in certain subgroups. The validated CV Risk SomaSignal® Test (SST) provides 4-year risk probability of MACE allowing for timely assessment of risk, but the shorter timescale makes comparison to 10-year PCE risk less intuitive.
PosterStatin signature: using proteomics to detect pharmacological fingerprints
Using a previously described metacohort (n=5,575) of patients with increased CV risk, we hypothesized that PCE would stratify patients differently than the CV Risk SST, and that CV Risk score scaled to 10 years would yield an improved net reclassification index (NRI).
PosterUsing a proteomics-based cardiovascular risk test to identify systemic changes in a clinical trial of nonalcoholic fatty liver disease
Improvement in hepaKc inflammaKon, NAFLD acKvity score and fibrosis were associated with improved proteomic CV risk scores regardless of treatment provided.