Human height: a model common complex trait

Abstract

Context Like other complex phenotypes, human height reflects a combination of environmental and genetic factors, but is notable for being exceptionally easy to measure. Height has therefore been commonly used to make observations later generalised to other phenotypes though the appropriateness of such generalisations is not always considered. Objectives We aimed to assess height’s suitability as a model for other complex phenotypes and review recent advances in height genetics with regard to their implications for complex phenotypes more broadly. Methods We conducted a comprehensive literature search in PubMed and Google Scholar for articles relevant to the genetics of height and its comparatibility to other phenotypes. Results Height is broadly similar to other phenotypes apart from its high heritability and ease of measurment. Recent genome-wide association studies (GWAS) have identified over 12,000 independent signals associated with height and saturated height’s common single nucleotide polymorphism based heritability of height within a subset of the genome in individuals similar to European reference populations. Conclusions Given the similarity of height to other complex traits, the saturation of GWAS’s ability to discover additional height-associated variants signals potential limitations to the omnigenic model of complex-phenotype inheritance, indicating the likely future power of polygenic scores and risk scores, and highlights the increasing need for large-scale variant-to-gene mapping efforts.

Keywords

• genetics
• genomics
• height
• gwas
• polygenic scores