Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, 1090 GE, Amsterdam, The Netherlands.
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.
Microbiome. 2023 Oct 9;11(1):222. doi: 10.1186/s40168-023-01669-w.
Host genetics can shape microbiome composition, but to what extent it does, remains unclear. Like any other complex trait, this important question can be addressed by estimating the heritability (h) of the microbiome-the proportion of variance in the abundance in 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, and not absolute, abundances, based on an underlying quantitative genetic model for absolute abundances. Based on this, we uncovered three problems that can arise when using relative abundances to estimate microbiome heritability: (1) the interdependency between taxa can lead to imprecise heritability estimates. This problem is most apparent for dominant taxa. (2) Large sample size leads to high false discovery rates. With enough statistical power, the result is a strong overestimation of the number of heritable taxa in a community. (3) Microbial co-abundances lead to biased heritability estimates.
We discuss several potential solutions for advancing the field, focusing on technical and statistical developments, and conclude that caution must be taken when interpreting heritability estimates and comparing values across studies. Video Abstract.
宿主遗传学可以塑造微生物组的组成，但在何种程度上塑造，目前尚不清楚。与任何其他复杂特征一样，这个重要问题可以通过估计微生物组的遗传力（h）来解决——即每个分类群丰度的方差中有多少归因于宿主遗传变异。然而，与大多数复杂特征不同，微生物组的遗传力通常基于相对丰度数据，其中特定分类群的丰度表示为样本中总微生物丰度的比例。
我们基于绝对丰度的定量遗传模型，为使用这种相对丰度而不是绝对丰度来估计微生物组遗传力，推导出了遗传力的分析近似值。在此基础上，我们揭示了当使用相对丰度来估计微生物组遗传力时可能出现的三个问题：（1）分类群之间的相互依存关系会导致遗传力估计不准确。对于优势分类群，这个问题最为明显。（2）样本量大会导致高假发现率。随着足够的统计能力，结果是在群落中遗传分类群的数量被强烈高估。（3）微生物共丰度会导致遗传力估计的偏差。
我们讨论了推进该领域的几种潜在解决方案，重点是技术和统计方法的发展，并得出结论，在解释遗传力估计值和比较不同研究中的值时必须谨慎。
