Gokhman David, Harris Keith D, Carmi Shai, Greenbaum Gili
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Department of Ecology, Evolution and Behavior, The Hebrew University of Jerusalem, Jerusalem, Israel.
Nat Commun. 2025 Jul 26;16(1):6898. doi: 10.1038/s41467-025-62355-z.
Predicting phenotypes from genomes is a major goal in genetics, but for most complex phenotypes, predictions are largely inaccurate. Here, we propose a more achievable alternative: relative prediction of phenotypic differences. Even with incomplete genotype-to-phenotype mapping, we show that it is often straightforward to determine whether an individual's phenotype exceeds a threshold (e.g., of disease risk) or which of two individuals has a greater phenotypic value. We evaluated prediction accuracy on tens of thousands of individuals from the same family, same population, or different species. We found that the direction of a phenotypic difference can often be identified with >90% accuracy. This approach also helps overcome some limitations in transferring genetic association results across populations. Overall, our approach enables accurate predictions of key information on phenotypes - the direction of phenotypic difference - and suggests that more phenotypic information can be extracted from genomic data than previously appreciated.
从基因组预测表型是遗传学的一个主要目标，但对于大多数复杂表型来说，预测在很大程度上是不准确的。在此，我们提出一个更可行的替代方法：表型差异的相对预测。即使基因型到表型的映射不完整，我们表明通常很容易确定个体的表型是否超过阈值（例如疾病风险阈值），或者两个个体中哪一个具有更大的表型值。我们在来自同一家族、同一人群或不同物种的数万人中评估了预测准确性。我们发现，表型差异的方向通常可以以超过90%的准确率被识别出来。这种方法也有助于克服在不同人群间转移遗传关联结果时的一些局限性。总体而言，我们的方法能够准确预测关于表型的关键信息——表型差异的方向——并表明可以从基因组数据中提取比之前认识到的更多的表型信息。
