The genetic basis of human height

Abstract

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.