The present study of 180,520 paired measurements from 86,037 complete twin pairs in 20 countries revealed that environmental factors shared by co-twins contribute to the inter-individual variation in height from infancy to early adulthood. The relative proportion of common environmental factors was greatest during the first years of life, representing almost half of the variation at age 1 and decreased over childhood and adolescence. The interpretation of these results, however, deserves some caution. It has been questioned whether twin studies are suitable for estimating heritability of height in infancy, since early growth patterns in twins differ considerably from singleton growth patterns25. Prenatal environmental factors can act very differently on MZ twins leading to differences in body size within pairs (the most extreme case is the twin-to-twin transfusion syndrome). This is an important issue because in the classical twin design heritability is estimated by comparing the resemblance of MZ and DZ twin pairs and thus body size differences in MZ pairs will result in lower heritability estimates. Since children may take several years to fully catch-up after birth, the high proportion of height variation explained by the shared environment in infancy may still reflect these prenatal environmental factors. Among other possible explanations, it might be that the shared environment represents the effects of gestational age or the effects of the higher measurement error (correlated in twins) at earlier ages.

The influence of the shared environment on height variation up to 19 years, which is consistent with previous studies in adolescents19 and adults21 with enough statistical power to detect this component, suggests that adult height variation reflects childhood living conditions. Studies have shown that the secular trend in adult height occurs during the first two years of life mainly due to increases in leg length26. A plausible explanation is that the period of most rapid growth, when the effect of an adverse environment is strongest, coincides with the period when most growth takes place in the long bones of the legs26. Multinational studies analyzing the genetic and environmental influences on body length segments, particularly leg length, are thus needed to disentangle the aetiology of total height variation. The small but considerable effect of unique environment on height variation, very similar across ages, may partly be due to measurement error, which is modelled as part of unique environmental factors. However, it is likely that it also reflects real environmental factors, for example, different exposure to childhood diseases.

A recent and large meta-analysis of twin correlations and variance components for 17,804 traits carried out separately in four age groups (0–11, 12–17, 18–64 and 65+ years) showed that the heritability estimate of height at 12–17 years was considerably greater than at 0–11 years27. Given the rapid growth that occurs in infancy, childhood and adolescence, in this individual-based pooled analysis we analyzed the heritability of height in one year age groups. We found that genetic contributions increase over childhood with heritability estimates in the range of previous studies in children and adults15,16,18,20,21. GWA studies have identified many common genetic variants for adult height. The most recent GWA meta-analysis in 253,288 individuals of European ancestry identified 697 genome-wide significant SNPs in 423 loci that together explained one-fifth of the heritability for adult height10. Further, in a study using whole-genome sequencing data from 44,126 unrelated individuals, all imputed variants explained 56% of variance for height suggesting that missing heritability is negligible for human height28. However, much less is known on the genetics of height in children. Van der Valk et al.29 found that polygenic scores based on 180 SNPs previously associated with adult height explained 2.95% of the variance of infant length and that of 180 known adult height loci, only 11 were genome-wide significantly associated with infant length.

The pattern of total height variation across ages was largely driven by genetic variance. The most consistent result is the increasing genetic variance with age, reaching its peak at around 13 years in girls and 14 years in boys. After that point, even if mean height continued to increase, genetic variance started to decrease in such a way that in late adolescence the magnitude was similar to that before pubertal events start. Adolescence is characterized by the onset of puberty and the occurrence of growth spurts. Although a secular and population-dependent decline has been observed in the age at onset of pubertal growth spurt and peak height velocity since the mid 1900s30,31, the pubertal height spurt generally begins at age 10–11 years in girls and 11–13 years in boys and reaches peak height velocity at about 12 years and 14 years, respectively13,30. In this study, twins within age groups are at various stages of puberty. In addition to the substantial heritability reported for pubertal timing32, a genome-wide genetic correlation (0.13) between age at menarche and adult height has also been found33. In fact, a genome-wide association meta-analysis showed that five loci associated with pubertal timing impacted multiple aspects of growth, both before and during puberty34. Therefore, it is possible that some of the genetic variance in height at these ages is confounded with genetic variance in pubertal events.

In spite of the largely similar age patterns observed in boys and girls, boys showed somewhat greater heritability estimates and genetic variation, especially in late adolescence. Greater heritability estimates in boys than in girls have previously been reported from birth through 19 years15 and in adulthood21. Moreover, some studies have shown a sex-specific genetic effect on height variation in adolescents19 and adults24. It is clear that both of the sex chromosomes are implicated in determining mean height. Short stature has been demonstrated in females with Turner syndrome who have only one X chromosome35 and taller stature seen in XYY men compared with XY men36. However, sex chromosomes have also been associated with height variation; for example, Gudbjartsson et al.37 identified 27 regions of the genome including a locus on X chromosome that together explained around 3.7% of the population variation in height. In our multinational data, the lowest genetic correlations within opposite-sex DZ pairs were found at 14–16 years of age and again at 18 years, suggesting that sex-specific genes have a role in the genetic variation of height not only during puberty, but also in late adolescence.

Comparison between geographic-cultural regions showed that mean height was greatest in Europe, somewhat shorter in North-America and Australia and shortest in East-Asia, but total variance was largest in North-America and Australia. Accordingly, genetic variation was also greatest in North-America and Australia and lowest in East-Asia. However, the relative proportions of additive and environmental variations were more similar in the different geographic-cultural regions. These results are consistent with a previous comparative twin study which found that the mean and variance of height were larger in Caucasian than in East-Asian populations in adolescence, but the heritability estimates were still at the same level19. An important proportion of the differences in total variances between geographic-cultural regions were attributable to genetic differences. It may be that allelic frequencies and effects of the genes involved in height vary between Europeans, North-Americans and Australians and East-Asians, leading to differences in genetic variation between the three population groups. A recent study across 14 European countries found that many independent loci contribute to population genetic differences in height and estimated that these differences account for 24% of the captured additive genetic variance38. However, a major part of the differences in genetic variation may also be because of gene-environment interactions modelled as part of the additive genetic component in our model. That is, the higher genetic variation observed in Caucasians could arise because there is a set of genes expressed more strongly in Western environments. For example, a study of adults of Japanese descent living in the United States and native Japanese found that Japanese men and women were shorter than Japanese-Americans, suggesting that environmental factors play a role in physical growth39. Analyzing this question in detail would require collection of twins or GWA studies in unrelated individuals with East-Asian origin living in a Western environment.

The study in Caucasian and East-Asian populations showed that approximately 91% of the differences in the total variance between these two population groups was attributable to genetic variances19. However, our study found that shared environmental variance also differed between geographic-cultural regions. The lower shared environmental variance observed in East Asian girls and greater in North-America and Australia during childhood may reflect cultural differences in terms of nutrition and other environmental resources. It is also important to note that we limited our East-Asian cohorts to affluent East-Asian populations including the Shandong and Guangdong provinces but excluding poorer areas of China. As reported previously, the heritability estimates of height were considerably lower and common environmental estimates higher in the poorer areas40, which may indicate larger differences between families in nutrition and infection history in these areas of China. This emphasizes the need to collect data on twins living under different environmental exposures.

The main strength of the present study is the very large sample size of our multinational database of twin cohorts, with height data from 1 through 19 years of age, allowing a more detailed investigation of the genetic and environmental contributions to individual differences in height during childhood and adolescence than in the previous studies. Twin participants are from 20 different countries, thereby making it possible to stratify the analyses by regions representing different ethnicities and environments. Important advantages of individual-based data are better opportunities for statistical modelling and lack of publication bias. However, our study also has limitations. The equal-environment assumption, upon which twin methodology is based, assumes that MZ and DZ twins are equally exposed to environmental factors relevant to the outcome. If equal-environment assumption is violated, it should be seen as differences in variances between MZ and DZ twins, but we did not find such evidence. In the classical twin design phenotypic assortment increases DZ correlations and thus inflates the common environmental component when not accounted for in the modelling. Assortative mating is well recognized for height and when the potential underestimation of heritability estimates was corrected using a sample of twins and their parents41, these authors showed that doing so increased the heritability estimates from 0.75 to 0.85. In our database we do not have information on parental height and thus could not take into account assortative mating, which may thus explain part of the shared environmental variation. A recent study showed that increased homozygosity, which is influenced by inbreeding, was associated with decreased height and that the effect sizes were similar across different continental groups and populations with different degrees of genome-wide homozygosity42. These authors thus suggested that homozygosity, rather than confounding as a result of environmental or additive genetic effects, directly contributes to phenotypic variance42. Further, most of the height measures were self-reported43, which are prone to error and can bias our analyses toward lower heritability estimates and higher estimates of unique environmental effects. Finally, countries and/or ethnic-cultural regions are not equally represented and the database is heavily weighted towards populations following the Westernized lifestyle; even when the large majority of the twin cohorts in the world participated in this project, our data still had limited power for East-Asia especially in adolescence. An even bigger problem is that there are few data available from South-Asia, Middle-East and Africa and no data from South-America. This demonstrates the need for new data collections in these regions.

Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments. Worthwhile objectives for future research are to study whether the same genetic and environmental factors contributing to height variation operate throughout time or new genes or new environmental factors start to operate at different ages and to analyze the heritability of growth in height. Further, a major challenge in future studies with more information on birth and pregnancy related variables is to explore the reasons for the low heritability of height at young ages.

In conclusion, environmental factors shared by co-twins exert their strongest influence on height variation in childhood, but these effects remain until the onset of adulthood. Genetic variation in height increased steadily during childhood and reached its peak at around 13 years in girls and 14 years in boys, which may be confounded with genetic variation in pubertal events. Especially in adolescence, there was a trend toward somewhat greater genetic variation in boys than in girls and part of the genetic variation of height was sex-specific. Genetic variation of height was larger in North-America and Australia and Europe compared with East-Asia, but the relative proportions of genetic and environmental variations between these three geographic-cultural regions were roughly similar. These findings suggest that, in spite of different ethnicities and environmental exposures, genetic factors play a major role on height variation in adolescence and early adulthood, but environmental factors shared by co-twins are also important.