Despite these challenges, quantifying human transcriptomic heritability is important. Although genes with significant eQTLs are, by definition, “heritable,” additional polygenic variation may be widespread and fail to reach statistical significance by standard genotype-expression association. Genes with substantial polygenic variation may also be subject to unique selection pressures not apparent from local eQTLs. The classical twin design, contrasting resemblance in monozygotic (MZ) to dizygotic (DZ) twin pairs, offers distinct advantages in interpretability and efficiency in heritability estimation.32
