Scientists estimate that about 80 percent of an individuals height is determined by the DNA sequence variants they have inherited, but which genes these variants are in and what they do to affect height are only partially understood. Some rare gene mutations have dramatic effects on height (for example, variants in the FGFR3 gene cause achondroplasia, a rare condition characterized by short stature). For most individuals, though, height is controlled largely by a combination of genetic variants that each have more modest effects on height, plus a smaller contribution from environmental factors (such as nutrition). More than 700 such gene variants have been discovered and many more are expected to be identified. Some of these variants are in genes that directly or indirectly affect cartilage in growth plates, which are areas in the long bones of the legs and arms where new bone is produced, lengthening the bones as children grow. The function of many other height-associated genes remains unknown.

In addition to the FGFR3 gene, researchers have identified hundreds of other genes involved in rare disorders that have an extreme effect on height. These genes (and the conditions they are associated with) include FBN1 (acromicric dysplasia, geleophysic dysplasia, Marfan syndrome), GH1 (isolated growth hormone deficiency), EVC (Ellis-van Creveld syndrome, Weyers acrofacial dysostosis), and GPC3 (Simpson-Golabi-Behmel syndrome). By studying the dramatic effect that altered versions of these genes have on height, scientists hope to better understand the complex interactions among genes that contribute to normal height. Some genes, such as ACAN, contain rare variants that cause severe growth disorders, and also other variants with milder effects on height in individuals without a related health condition. Identifying other height genes, and variants with large or small effects, is an active area of genetic research.

Because height is determined by multiple gene variants (an inheritance pattern called polygenic inheritance), it is difficult to accurately predict how tall a child will be. The inheritance of these variants from ones parents helps explain why children usually grow to be approximately as tall as their parents, but different combinations of variants can cause siblings to be of different heights. Height is influenced by other biological mechanisms (such as hormones) that may also be determined by genetics, although the roles of these mechanisms are not fully understood.

In addition to genetic and biological determinants, height is also influenced by environmental factors, including the nutritional status of the mother during pregnancy, whether she smoked, and her exposure to hazardous substances. A well-nourished, healthy, and active child is likely to be taller as an adult than will be a child with a poor diet, infectious diseases, or inadequate health care. Socioeconomic factors such as income, education, and occupation can also influence height. In some cases, ethnicity plays a role in adult height, but studies on immigrant families have shown that moving to a country with better access to nutritious food, healthcare, and employment opportunities can have a substantial influence on the height of the next generation; this suggests that some differences in height between ethnicities are explained by non-genetic factors.

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Marouli E, Graff M, Medina-Gomez C, Lo KS, et al. Rare and low-frequency coding variants alter human adult height. Nature. 2017 Feb 9;542(7640):186-190. doi: 10.1038/nature21039. Epub 2017 Feb 1. PubMed: 28146470. Free full-text available from PubMed Central: PMC5302847.

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