Introduction
In the pediatric endocrine clinic, parents often ask: What determines a person's height? My husband and I are not tall, and the child is not tall now. Can we change the genetics? Children see a doctor every year and do a good job in diet, exercise, sleep and psychology. Why can they still only reach genetic height? How much does a person's height and heredity play? I take my child to see his height every year, hoping to break through heredity... So, can we break through heredity?
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people's height is determined by genetics?
How many genes are related to height?
Height is the sum of genetic factors and environmental factors GIANT study: The largest height study of genetic height so far Height varies from person to person, and genetics and nutrition are the key factors. How much does genetic play a role in human height?
How to calculate how much height can improve environmental factors increase? Does
mean that all efforts outside of genetics are futile?
people's height is determined by genetics?
In many formal and informal occasions, I hear the same voice, "70% of a person's height is determined by heredity." However, no director or expert would explain how this 70% came about, and never see the source of the data research. 70%? Confirm? Why not 60%, or 80%,? How did 70% come from? Could it be the slander of "Three points are destined to heaven, and seven points are determined by hard work"?
Scholars have a problem, that is, they like to be serious, and unfortunately, so do I. Readers who are familiar with me know that most of my views on popular science articles have authoritative sources, and are not just my personal views ( unless otherwise specified ). In addition, important numbers in the article must have a source. The purpose of this is to avoid from passing incorrect medical information to readers due to personal prejudice .
However, it has to be admitted that in terms of the question of how much a person's height is determined by heredity, "70% determined by heredity" comes from countless "teachings" by his predecessors, and he has never been serious about it. Today, let’s take a closer look at this topic. Why be serious? Because this issue is very important, if height is entirely determined by genetics, then there is no need to struggle, just lie down and forget about it; if medical intervention cannot change genetics, why should we increase the risk of medication?
How many genes are related to height?
Some rare genetic mutations have a significant impact on height. For example, FGFR3 gene mutations can cause cartilage underdevelopment , a rare disease characterized by short stature and short limbs; the loss of exons of the SHOX gene can also lead to short stature; Turner syndrome (45,X) can also lead to short stature, and is the only chromosomal monomer syndrome that can survive or exist in humans. The appearance phenotype is female, but the chromosome is one less than normal women. The short stature of this syndrome may be related to insufficient SHOX haploid dose; in addition, Prader-Willi syndrome, Russell-Silver syndrome, 3M syndrome, Noonan Syndrome can also lead to severe short stature...
For most healthy individuals ( is understood as "healthy short" or "naturally short" ), height is largely controlled by the combination of gene mutations ( that is, polygenic inheritance ), and the impact of each genetic mutation on height is relatively mild . At present, more than 700 such genetic mutations have been discovered in . is related to height. It is expected that more genetic mutations will be found in .
For individuals with short pathological stature ( is understood as "sick short" ), in addition to the FGFR3 gene, researchers have also discovered hundreds of other genes related to rare diseases, and these genes have extreme effects on height . These genes include the FBN1 gene (acromum dysplasia, brain dysplasia, Marfan syndrome), the GH1 gene (solute growth hormone deficiency), EVC (Ellis-van Creveld syndrome), Weyers acrofacial dysplasia and GPC3 gene (Simpson-Golabi-Behmel syndrome), and so on.
If there are mutations in these genes, height will not follow the rules of genetic target height and will be very short. By studying the significant impact of mutations in these genes on height, scientists can better understand the complex interactions between genes that affect normal height.
height belongs to polygenic inheritance. If parents are taller, the children will also be taller; if parents are shorter, the children will also be shorter; if parents are taller and shorter, it depends on whose genes are dominant. The children may be tall, shorter, or middle-aged. So, how to calculate the height of a child when he is an adult based on his parents' height? That is, the calculation of the genetic target height. The formula is as follows:
In clinical practice, we use the first formula more often, namely CMH method :
- For example, the father is 173cm tall and the mother is 160cm tall. The son's genetic target height = (173+160+13)/2±5cm = 173±5cm, that is, the son's adult life height is 168~178cm, both belong to the genetic range.
- The daughter's genetic target height is = (173+160-13)/2±5cm = 160±5cm, which means that the daughter's adult life height is between 155 and 165cm, both of which are within the genetic range.
Height is the sum of genetic and environmental factors
However, it should be emphasized that since height is determined by multiple gene mutations ( ie, polygenetic genetic ), it is difficult to accurately predict a child's height. These variations inherited from parents help explain why children usually grow almost as tall as their parents, but different combinations of variations may lead to different heights of siblings. height is affected by other biological mechanisms ( such as the hormone ), which may also be determined by genetics, although the role of these mechanisms is not fully understood.
In addition to genetic and biological determinants, height is also affected by environmental factors, including the mother's nutritional status during pregnancy, whether she smokes, and whether she is exposed to harmful substances. In addition, nutritional and psychosocial factors after birth may also affect children's height. A well-nourished, healthy and active child may be higher in adulthood than a child with poor diet, infectious diseases or inadequate health care. Socio-economic factors such as income, education, and occupation can also affect height.
In some cases, racial factors also have an impact on adult height, but research on immigrant families has shown that immigrating to a country with better access to nutritious food, health care and employment opportunities can have a significant impact on the height of the next generation. This shows that some differences in height among ethnic groups in can be explained by non-genetic factors.
GIANT Research: The largest genetic study on height to date
This is the largest genome-wide association study (GWAS) to date, involving more than 300 institutions and more than 250,000 research subjects, and the number of known gene regions affecting height is about 400. This study, conducted by the International Alliance for Genetic Survey of Anthropometric Characteristics (GIANT), has given people a better understanding of height biology and provides a model for studying characteristics and diseases caused by the combined effects of many common genetic changes. The results of this study were published online by Nature Genetics on October 5, 2014.
"Height is almost entirely determined by genes, but our early studies can only explain about 10% of the effects of this gene," said Joel Hirschhorn, MD, MD, of Boston Children's Hospital, MIT Broad Institute and Harvard , and a leader of the GIANT Alliance and a senior co-investor in the study.“Now, by double the number of people participating in our study, we have a more comprehensive understanding of how common genetic mutations affect height—how many genetic mutations are there, and how much they affect height.”
Hundreds of GIANT researchers analyzed genomic data from 253,288 people (250,000). They examined about 2 million common genetic variants. From this gene library , they identified 697 variants (in 424 gene regions) related to height, which is by far the largest number associated with any trait or disease. "We can now explain 20% of the genetic factors of height, compared to 12% before," said Tono Esco, Ph.D., one of the first authors of the study report of the Boston Children's Hospital, the Broad Institute and the University of Tartu ( Estonia ). "We can now explain 20% of the genetic factors of height, compared to 12% before."
By studying height, we understand how the body affects a shape through multiple genes. height is easy to measure, and it is estimated that 80% of the height variation is genetic (prerequisite: in developed countries with sufficient nutrition and complete medical insurance, healthy individuals) .
Previous large-scale genome-wide association study (GWAS) showed that a large number of genes affected height and showed that most of the heritability of comes from common genetic variants, rather than rare genetic variants. The former affects the height of normal people, while the latter not only affects height, but also causes diseases. Since the sample size is not enough to draw a clear conclusion, the GIANT team established the largest sample size to date.
Senior researcher at the University of Exeter, UK, said: "In 2007, we published our first paper, the first to identify the genes that affect height, and now We have identified nearly 700 genetic variants related to determining height. "
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Many of the genes they also found are likely to be important regulators of bone growth, and some may also lead to unexplained skeletal growth abnormal syndrome in children. For example, the mTOR gene is known to be associated with cell growth, but has not been previously associated with human skeletal growth. Other genes that have been proven to be important include genes related to metabolism of collagen (a component of bone ) and chondroitin sulfate (a component of cartilage ), as well as gene networks active in growth plates ( near the end of the long bone).
Height varies from person to person, inheritance and nutrition are the key factors
It is reported that the tallest person in the world is 2.72 meters (Robert Wadlow), while the shortest person is only 67 cm (26 inches). Some people think that height is unchangeable, which is determined by the genetic makeup of our conception. After all, tall parents usually give birth to tall children and vice versa.
genetics expert from the University of Queensland, Australia, Professor Peter Visscher said: "There is a lot of evidence that as the country becomes industrialized and becomes richer, height increases over time, and this change must be caused by environmental factors, because genetic factors do not change in a short period of time (such as decades)." he went on to say, "The possible specific environmental factors are abundant food and better health care."
Multiple case studies highlight how diet affects height. Professor Saverio Alberti, a geneticist at the University of Messina in Italy, said: "The height of newborns during the Dutch famine in 1944 may be a suitable example. Children born or raised in this famine are 4 cm shorter than the average height of the Dutch at that time."
It is generally believed that about 80% of the height is genetically affected. Your DNA determines your maximum potential height, and environmental factors determine whether you have reached this maximum. Therefore, in countries where children are generally malnutrition, it is difficult to predict height from genes alone.On the other hand, in countries with adequate nutrition, it is possible to use genes to predict height, closest to 3cm.
people's height, how much does genetic play?
The question can be rewritten as: "How many height differences (differences between individuals) are caused by genetic influence, and how many are caused by nutritional influence?" The simple answer to this question is that about 60% to 80% of individual height differences in are determined by genetic factors, while 20% to 40% can be attributed to environmental impacts, mainly nutrition and disease (other factors have little impact) .
human height is a quantitative trait , that is, a quantitative trait controlled by multiple genes and environmental factors. Many studies estimate the heredity of human height. Typically, these studies determine heritability by estimating the degree of similarity between relatives. One can distinguish genetic effect from environmental effects by linking the genetic similarity of relatives (twins, siblings, parents and offspring) with height similarity.
To accurately measure gene similarity, we can measure the number of gene markers they share. For example, Peter M. Visscher of the Queensland Institute of Medical Research recently reported that has a heritability rate of 80% in height based on 3375 studies of Australian twins and siblings. This estimate is considered impartial because it is based on a large twin and sibling population as well as an extensive survey of genetic markers.
In the United States, the heredity rate of white men is estimated to be 80%. These estimates were strongly supported by another study of 8798 of Finnish twins, in which hereditary rate was 78% for men and 75% for women. Other studies have shown that the heredity rate of white people is even higher than 80%.
However, because the populations of different ethnic groups have different genetic backgrounds and different living environments, height heritability varies in different regions and races. Among the Asian population, the heredity rate of height is much lower than 80%. For example, In 2004, Miao-Xin Li, et al. of Hunan Normal University in China, estimated that their height heritability rate was 65% based on data from 385 families in China. has a low heredity rate in the African population. According to a 1978 study by D. F. Roberts, who worked at Newcastle University in the UK at that time, the height heritability rate of West African population was 65% .
This genetic diversity is mainly due to the genetic background of different ethnic groups and different environments (climate, eating habits and lifestyles). Among them, the better the race's height inheritance rate, the lower the heredity rate of race with poor nutrition. The data on the heredity rate of China's population is based on the improvement of people's living standards in 2004, especially in coastal cities. The nutritional conditions are almost no different from those in developed countries, so the increase in heredity rate is expected.
How to calculate how much height can improve the environmental factors?
Heraldity allows us to study how genes directly affect individual height. For example, white men have an inheritance rate of 80%, and their average height is 178 cm. If we meet a 183 cm tall white man on the street, heritability tells us how much of his extra height is caused by genetic mutations, and how much is caused by his environment ( eating habits and lifestyle ) . This person is 5 cm taller than the average height. Therefore, of the 5 cm or 4 cm that increases, 80% are genetic variations, while 1 cm is environmental impacts such as nutrition.
If the height of the parents is known, heritability can also be used to predict the height of an individual.For example, a man with a height of 175 cm married a woman with a height of 165 cm and they all came from the Chinese population, with an average height of 170 cm for men and 160 cm for women. We can predict their children's height, assuming that the heredity rate for men in this population is 65% and for women 60%.
For boys, the difference between expected height and the overall mean is =0.65 x[(175 - 170)+(165 - 160)] / 2, equal to 3.25 cm; if it is a daughter, the difference is =0.6 x[(175 - 170) +(165 - 160)]/ 2, equal to 3cm; therefore, the expected height of the son is 170 + 3.2 (173.2cm), and the expected height of the daughter is 160 + 3 (163cm); environmental impact will increase the height of the son by 1.75cm=0.35 x[(175 - 170)+(165 - 160)] / 2; Environmental impact will increase the height of the daughter by 2cm=0.4 x[(175 - 170) +(165 -160)] / 2.
Of course, the heritability rate is 60%, using the 2004 research data. Assuming that the heritability rate of coastal cities is similar to that of developed countries, and the heritability rate of both men and women reaches 75%, which is still the case above. Let’s calculate it again:
The expected height of boys and girls is the difference between the overall mean and the difference between the overall mean is =0.75 x[(175 - 170)+(165 - 160)] / 2, which is equal to 3.75 cm; therefore, the expected height of the son is 170 + 3.75 (173.5cm), and the expected height of the daughter is 160 + 3.75 (163.75cm); environmental impact will increase the height of the son/daughter by 1.25cm=0.25 x[(175 - 170) +(165 - 160)] / 2.
That is to say, the better the environmental factors ( is mainly nutrition, medical care and illness ), the higher the heredity rate of height, and vice versa. Therefore, it can be said that height is largely determined by genetics, and what we do has little impact on height improvement. Of course, these predictions only reflect the average expected height of the two siblings, and the actual observed height may be different.
Through these calculations, we realize that in China, the environment ( is mainly a nutrient ) can only change the height of a given offspring about 2 cm. Of course, this is a positive statement. If it is due to a serious disease, it may be farther from the genetic height. Therefore, in the diagnosis and treatment work, doctors pay more attention to whether short-body children are "pathologically short" due to illness, while tend not to interfere with "natural shortness".
Does it mean that all efforts outside of inheritance are futile?
Does this mean that no matter what happens to the child’s environment, the change in height will not exceed this? Can special treatments and nutritional supplements further increase height? The answer is yes, ensuring balanced nutritional intake is the basic condition for growing taller.
Therefore, malnutrition in childhood is harmful to height. However, it should also be suggested that overnutrition, especially obesity, will lead to an accelerated bone age and increase the incidence of precocious puberty, which will be harmful to height. Generally speaking, boys reach their maximum height at the age of eighteen or nineteen, while girls reach their maximum height at the age of fifteen or sixteen. Therefore, adequate nutrition before adolescence is crucial to height.
In addition, although childhood diseases can affect final height, recombinant human growth hormone treatment can make up for this growth defect ( is mainly suitable for growth hormone deficiency ). However, improves height through this treatment and cannot be predicted based on heritability.
There are two reasons: First, the heritability of populations treated with growth hormone has not been estimated. Second, genes and growth hormones can work together to affect height, which means that their effects may not simply superimpose each other, but multiply the final effect.
Of course, it should be specifically mentioned that the use of recombinant human growth hormone has strict indications and needs to be strictly evaluated by doctors. You cannot blindly use for height, especially for children whose height does not meet the dwarf standard ( just does not meet the expected height of their parents or their genetic height ), which can be said to be abused and has a greater risk of medication.
However, the question is why different groups with similar genetic backgrounds may have different heritability. As early as high school biology class, the teacher told us that phenotype = genotype + environmental factors, so the answer is of course environmental impact. When a given environment maximizes the genetic potential of a particular trait of a population, that population tends to have a higher heritability to that trait and vice versa.
In developed countries, children need to develop rich in nutrients, which will maximize the genetic potential of height if there is no choice or new mutation. Therefore, the overall heritability rate is often estimated to be higher, i.e. 80%. In contrast, in developing countries , nutritional deficiency leads to a lower heredity rate.
The fact that the average height of the U.S. population has almost flattened over the past decade, suggesting that the nutritional environment has almost maximized the genetic potential of height, at least in this country. Improving nutrition elsewhere may have similar benefits in height.
In China's coastal cities, the nutritional level is close to that of developed countries, so it is likely that the heritability rate has reached about 80%.
- References -
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