Abstract Host genetics can shape microbiome composition, but to what extent it does, remains unclear. Like any other complex trait, this question can be addressed by estimating the heritability ( h 2 ) of the microbiome – the proportion of variance in the abundance of each taxon that is attributable to host genetic variation. However, unlike most complex traits, microbiome heritability is typically based on relative abundance data, where taxon-specific abundances are expressed as the proportion of the total microbial abundance in a sample. We derived an analytical approximation for the heritability that one obtains when using such relative abundances and we uncovered three problems: 1) The interdependency between taxa leads to imprecise heritability estimates. 2) Large sample size leads to high false discovery rates, overestimating the number of heritable taxa. 3) Microbial co-abundances lead to biased heritability estimates. We conclude that caution must be taken when interpreting heritability estimates and comparing values across studies.

Relative abundance data can misrepresent heritability of the microbiome