Twin Study Provides Heritability Estimates for 2321 Plasma Proteins and Assesses Missing SNP Heritability

Assessing how much variability in blood plasma proteins
is due
to genetic or environmental factors is essential for advancing personalized
medicine. While large-scale studies have established SNP-based heritability
(SNP-h2) estimates for plasma proteins, less is known about
the proportion of total genetic effects on protein variability. We
applied quantitative genetic twin models to estimate the heritability
of 2321 plasma proteins and to assess the proportion of heritability
accounted for by SNP-h2 estimates. Olink proteomics data
were generated for 401 twins aged 56–70, including 196 complete
same-sex twin pairs. On average, 40% of protein variability was attributable
to genetic effects. Twin-based heritability estimates were highly
correlated with published SNP-h2 estimates from the UK
Biobank (Spearman coefficient: ρ = 0.80). However, on average,
only half of the total heritability was covered by SNP-h2, and the other half, representing one-fifth of the total protein
phenotypic variability, remains missing.