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The genetics of height

Medicover Genetics Editorial Team |
October 26th 2022

Prospective parents often wonder what their child will look like. What eye or hair color will they have? Will they look more like them or their partner? Among these questions, height is also a frequently asked trait. Several factors can impact the height of a child including both parents’ height, genetics, and environmental factors.

Predicting a child’s height

There is no proven way to predict a child’s future height. However, several formulas can provide a reasonable guess for child growth [1]. The best predictor of a child’s height is their parents’ height or, more specifically, the mid-parental height. The mid-parental height is calculated by adding the mother’s and father’s height, adding 13 cm (5 inches) for boys or subtracting 13 cm (5 inches) for girls, and then finally dividing by 2. Most children will reach an adult height within 2 inches of the mid-parental height. Another way to estimate a child’s adult height is to double a boy’s height at age 2 or a girl’s height at age 18 months.

Genetics

The study of height has a long-standing tradition in genetics. Interestingly, the field of quantitative genetics originated from studies of human height in the late 19th and early 20th centuries [2]. 

Genetic variation

Scientists estimate that about 80 % of an individual’s height is determined by the DNA sequence variations they have inherited, but which genes these changes are in and what they do to affect height are only partially understood [3]. DNA sequence or genetic variation is a term used to describe the variation in the DNA sequence in our genomes and results from subtle differences in our DNA [4]. Genetic variation is what makes us unique, whether in terms of hair color, skin color, or even the shape of our faces. Individuals of a species have similar characteristics but they are rarely identical, the difference between them is called variation.

Single nucleotide polymorphisms (SNPs, pronounced ‘snips’) are the most common type of genetic variation among people. Each single nucleotide polymorphism represents a difference in a single DNA base (A, C, G, or T), in a person’s DNA. On average they occur once in every 300 bases and are often found in the DNA between genes.

Inheritance pattern

In 1918, Fisher calculated the first heritability estimate of height [5]. He described it as “the proportion of total variation explained by genetic variation”. In his paper, he demonstrated that continuous characters are caused by a combination of many genetic loci with small effects (polygenic inheritance).

polygenic inheritance pattern is considered since height is determined by multiple gene variants. This type of inheritance pattern makes it difficult to accurately predict how tall a child will be. However, the inheritance of these variants from one’s parents helps explain why children usually grow to be approximately as tall as their parents. Different combinations of variants can cause siblings to be of different heights. 

Latest studies

In a recent study [6], researchers conducted a Genome-Wide Association Study (GWAS). In these types of studies, whole genomes in a population are scanned to identify associations between genetic variants and traits. Their analysis revealed 12,111 common single nucleotide polymorphisms (SNPs), places in the genome where a single letter varies, that were associated with height. 

Together, the SNPs account for 40 % of all variation in height for individuals of European ancestry, and 10-20 % of variation for people of non-European ancestry. This difference is due to the composition of the GIANT study cohort, which is mostly of European ancestry. This lack of diversity is a known and common problem in genetic studies. But in the GIANT study, more than one million participants were of East Asian, Hispanic, African, or South Asian ancestry, a number the team says is higher than other GWAS.

The researchers say that across the different populations, so far, they have found that the same regions of the genome influence height. They emphasize, however, that including more people of non-European ancestry will be critical to increasing prediction accuracy and could help identify genetic variants specific to certain groups.

Clinical implication

These SNPs could help researchers develop better height-prediction tools for use in clinics. Pediatricians currently predict how tall a child will be based on their family history, but these estimates aren’t perfect. For example, they don’t predict different heights for a pair of siblings. A prediction based on SNPs could potentially be more accurate. If a physician noticed that a child’s height didn’t match a prediction, that could be a clue to test the child for rare hidden conditions that affect growth such as Celiac disease and hormone deficiencies. 

Genomic regions identified 

GIANT’s findings showed that SNPs influencing height clustered within regions covering just over 20 % of the genome. In particular, the SNPs were near genes previously associated with skeletal growth disorders; 25, for instance, clustered near the ACAN gene, which is mutated in patients with short stature and a condition called skeletal dysplasia. Several SNPs also implicate signaling pathways that impact skeletal growth plates — cartilage near the ends of long bones that expands and hardens into solid bone as a child grows. 

The researchers believe this clustering of genetic variants likely applies to other traits and could inform the study of other common conditions, such as high blood pressure or asthma, that are influenced by multiple genes. 

Summary

Researchers analyzed data from nearly 5.4 million people and identified more than 12,000 genetic variants that influence height. These variants explain 10 to 40 % of all variation in height depending on a person’s ancestry and cluster around parts of the genome involved in skeletal growth.

The findings, published in Nature, could one day help physicians identify individuals who aren’t reaching their genetically predicted height and might have a hidden disease or deficiency affecting their growth and health. 

Environmental factors and nutrition

In addition to genetic and biological determinants, height is also influenced by environmental factors, including a mother’s nutrition 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.

Congenital disorders

Some rare gene variants have dramatic effects on height. One of these conditions is achondroplasia which is a rare hereditary bone growth disorder, characterized by short stature and caused by variants in the FGFR3 gene [3]. Another congenital disorder that can cause short stature is known as Turner syndrome. This rare condition causes delays in puberty. Unlike achondroplasia, Turner syndrome doesn’t run in families.

Other congenital disorders lead to a taller-than-normal stature. These include Marfan and Klinefelter syndromes. Marfan syndrome is caused by variants in the FBN1 gene leading to connective tissue enlargements, while Klinefelter syndrome occurs when males are born with an additional copy of the X chromosome.

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.

Hormonal considerations

During puberty, hormones are essential for regulating body growth. These include thyroid hormones, human growth hormones, and sex hormones such as testosterone and estrogen. Any abnormalities in these hormones could alter growth as well as your overall height. Children who develop hypothyroidism (low thyroid) or pituitary gland disorders may experience shorter than average height compared to their parents.

Rarely, hormonal disorders can contribute to being taller than normal. For example, gigantism is caused by too many human growth hormones produced by pituitary gland tumors.

Gender

Height is also a classic example of a sexually dimorphic trait; on average, men are taller than women in all human populations [2]. Globally, the mean height of women is about 12 cm (4.5 inches) shorter than that of men [7]. In the latest available data, the global mean height for men was 171 cm, versus 159 cm for women. This height disparity between the sexes is present everywhere in the world. 

In a recent study [8], the researchers discovered that a combination of sex-biased genes accounts for approximately 12 % of the average height difference between men and women. This finding demonstrates a functional role for sex-biased gene expression in contributing to sex differences. 

Having the same gene expressed at different levels in each sex is one way to perpetuate sex differences in traits despite the genetic similarity of males and females within a species — since except for the second sex chromosome (the Y in males or the second X in females), the sexes share the same pool of genes. For example, if a tall parent passes on a gene associated with an increase in height to both a son and a daughter, but the gene has male-biased expression, then that gene will be more highly expressed in the son, and so may contribute more height to the son than the daughter.

The study concluded that sex-biased gene expression contributed approximately 1.6 cm to the average height difference between men and women, or 12 % of the overall observed difference.

Conclusion

An individual’s height is primarily determined by genetics (about 80 %). However, other factors, including environmental factors, nutrition, congenital conditions, and gender also influence height.

References

[1] Mayoclinic. What’s the best way to predict a child’s adult height? Retrieved 25 October 2022 from https://www.mayoclinic.org/healthy-lifestyle/childrens-health/expert-answers/child-growth/faq-20057990

[2] Jelenkovic A et al. Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts. Sci Rep. 2016 Jun 23;6:28496. doi: 10.1038/srep28496. PMID: 27333805; PMCID: PMC4917845. https://www.nature.com/articles/srep28496

[3] MedlinePlus. Is height determined by genetics? Retrieved 25 October 2022 from https://medlineplus.gov/genetics/understanding/traits/height/

[4] yourgenome. What is genetic variation? Retrieved 25 October 2022 from https://www.yourgenome.org/facts/what-is-genetic-variation/

[5] Fisher, R. (1919). XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance. Transactions of the Royal Society of Edinburgh, 52(2), 399-433. https://doi.org/10.1017/S0080456800012163

[6] Yengo L et al. A saturated map of common genetic variants associated with human height. Nature. 2022 Oct 12. doi: 10.1038/s41586-022-05275-y. Epub ahead of print. PMID: 36224396. https://www.nature.com/articles/s41586-022-05275-y

[7] Our World in Data. Human Height. Retrieved 25 October 2022 from https://ourworldindata.org/human-height

[8] Naqvi S et al. Conservation, acquisition, and functional impact of sex-biased gene expression in mammals. Science. 2019 Jul 19;365(6450):eaaw7317. PMID: 31320509; PMCID: PMC6896219. https://www.science.org/doi/10.1126/science.aaw7317

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