Extended Data Fig. 7: Effect of TREM2 missense variants on TREM2 measurements by SomaScan and ELISA.
From: Large-scale integration of the plasma proteome with genetics and disease
Estimate of the specificity of the sTREM2 levels in SomaScan. TREM2 levels in plasma measured by SomaScan versus TREM2 measured by ELISA on the same sample, coloured by genotype of the TREM2 R47H missense variant, rs75932628, or by genotype of the TREM2 R62H missense variant, rs143332484 (there were no compound heterozygotes). The six individuals that are homozygous for either Arg47His or Arg62His have extremely low levels of TREM2 measured by SomaScan compared to non-carriers inconsistent with the measurements by ELISA. Heterozygotes for either variant also have lower levels that non-carriers when measured by SomaScan but not when measured by ELISA. We conclude that the observed association of Arg47His allele with TREM2 levels based on SomaScan is an artefact due to altered conformation of TREM2 mediated by the coding change leading to a reduced affinity of the SomaScan aptamer targeting TREM2.
