Bicknell Louise S, Hirschhorn Joel N, Savarirayan Ravi
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
Nat Rev Genet. 2025 Apr 7. doi: 10.1038/s41576-025-00834-1.
Human height is a model polygenic trait - additive effects of many individual variants create continuous, genetically determined variation in this phenotype. Height can also be severely affected by single-gene variants in monogenic disorders, often causing severe alterations in stature relative to population averages. Deciphering the genetic basis of height provides understanding into the biology of growth and is also of relevance to disease, as increased or decreased height relative to population averages has been epidemiologically and genetically associated with an altered risk of cancer or cardiometabolic diseases. With recent large-scale genome-wide association studies of human height reaching saturation, its genetic architecture has become clearer. Genes implicated by both monogenic and polygenic studies converge on common developmental or cellular pathways that affect stature, including at the growth plate, a key site of skeletal growth. In this Review, we summarize the genetic contributors to height, from ultra-rare monogenic disorders that severely affect growth to common alleles that act across multiple pathways.
人类身高是一种典型的多基因性状——许多个体变异的累加效应导致了这一表型的连续、由基因决定的变异。身高也会受到单基因疾病中单基因变异的严重影响，相对于人群平均水平，这些变异通常会导致身材发生严重改变。解读身高的遗传基础有助于理解生长生物学，并且与疾病也相关，因为相对于人群平均水平，身高的增加或减少在流行病学和遗传学上都与患癌风险或心脏代谢疾病的改变有关。随着近期关于人类身高的大规模全基因组关联研究趋于饱和，其遗传结构已变得更加清晰。单基因和多基因研究涉及的基因都集中在影响身高的共同发育或细胞途径上，包括生长板，这是骨骼生长的关键部位。在本综述中，我们总结了影响身高的遗传因素，从严重影响生长的超罕见单基因疾病到作用于多种途径的常见等位基因。
