Is there really a tyrant gene? A genome-wide association study found some genetic variants related to academic achievement, but each of these mutations exerts a very limited influence individually. A genome-wide association study found mutations that may have an effect on the complex behavior of everyone's academic attainment.

Basic research on genetics of human behavior has always been a controversial research direction. For example, some people have studied identical twins and nonidentical twins, trying to predict how much genetic mutations will affect their differences in income and years of education (in other words) That is to say, when trying to study the heritability of these people entering university and becoming rich), some people think that such research is meaningless, and it should be prohibited from testing heritability for social and economic achievements. And research. However, Rietveld and others claimed that they have made some new progress in this area and discovered genes related to everyone's academic achievement. Similar news will appear one or two every once in a while, but in the end it is always confirmed to be false news, so how should we face and interpret this scientific research discovery?

Like complex traits such as height and weight, this trait of behavior is likely to be a trait that is partially affected by the overall effect of hundreds of thousands of genetic elements that have little effect. Someone once tried to find these genetic elements by studying a whole family member, but in the end it failed. They have searched for genetic markers that are coinheritance (coinheritance); they have also studied candidate genes that are related to known neurobiological traits, or may be related to these neurobiological traits, but basically no Can be successful. Genome-wide association studies can detect whether a certain trait is related to a mutation in hundreds or even millions of mutations. At present, there is basically a consensus on genome-wide association research, that is, this method is very useful for non-behavior traits, but it needs to be reminded that this method can only find a few mutation sites, and cannot find Out all relevant sites. But apart from a few good luck, in the analysis of weight, height and certain diseases, genome-wide association studies are almost nothing.

This may be because the behavior is not the same as other traits, it is not genetically regulated. For autism and schizophrenia, a large portion of the genetic defects that cause disease may be very rare mutations, and some of these mutations may be suddenly new, so it is impossible to pass genome-wide association studies at all. Discover them. Using genome-wide association studies can only find known, relatively common mutations. In addition, the genetic impact of these mutations on behavior is very small, much smaller than we expected, and the number of such mutations is much more than we expected, so it is difficult for us to find these large numbers, but the effect is Insignificant genetic mutation.

However, the research of Rietveld and others has gained some results and provided us with some answers. They found that those mutations related to academic achievement (mainly measured by the number of years of education and completion of university studies), the impact of each mutation is very small. The effect of these mutations is much smaller than the effect on physiological traits. Only when the test sample is very large (a total of 126,000 people were analyzed in this research work) can the effect of these mutations be discovered. Among them, the effect of the most influential mutation is only 0.02%, while the effect of the mutation that has an impact on height is about 0.4%, and the effect of the mutation that has an effect on weight is about 0.3%, compared with a whole. Magnitude. But this finding alone is not enough to explain the overall effect of all these mutations. Therefore, it is particularly important to conduct another observation test.

We assume that only 10 genetic loci are related to academic achievement, and the signals of these 10 loci are also ranked in the top ten in genome-wide association studies, and we also assume that the influence of each locus is The largest one can reach 0.02%. So if all the signals at these 10 sites are taken into account and they are regarded as a whole predictor, how much influence will this predictor have on academic achievement? In fact, this This is the so-called polygenic score method. If the 10 sites we selected are really effective sites, then their overall effect should be 10 × 0.02, which can reach 0.2%. If you magnify this number, assume there are hundreds or thousands , Or more sites have played a role, then their effect is very powerful, enough to explain the effect of genetics on behavioral traits. However, if there are really only 10 sites at work, it will not actually have any substantial impact, but it will synthesize the role of other sites. As Rietveld et al. Discovered, the more mutations involved in the function, the more accurate the prediction of the effect. This means that academic achievement really seems to be a trait influenced by multiple genes.

But why is the influence of these sites so small? Is it because our behavioral detection methods are too poor to detect the real influence? The work of Rietveld et al. Has confirmed this to some extent. Rietveld believes that if we can make full use of various phenotypic detection methods, such as years of education, then genome-wide association research may also play a role in helping us find genes related to a broader social association. Then you can combine some other relevant information, even if it is not yet certain information, to further analyze these genes.

The method used in genome-wide research to discover candidate genes is of practical significance. In fact, we have found that the degree of smoking is related to the mutation of the long arm of chromosome 15, which is found through the investigation of the number of smoking in a large number of people. We can carry out very accurate detection of this phenotype, but the actual exposure of tobacco and other indicators can only be non-quantitatively tested, mainly because everyone has different degrees and ways of smoking, such as Some people will smoke deeply into their lungs, and some people like to smoke the cigarette all the time, leaving nothing at all. Since the consumption of nicotine is most likely to be affected by genetic factors, many direct methods of detecting nicotine can more accurately detect the influence of genetic factors, and can also clarify the possible association mechanisms.

The indicator of years of education has made Rietveld and others feel the importance of finding suitable trait detection methods. For academic achievement of this trait, we can have many detection methods. Sometimes a short questionnaire survey is finished, sometimes it will be Do a very detailed assessment. However, there is no evidence to prove that the effectiveness of the genetic effects detected using the rougher detection methods is weaker than when using the precise detection methods. Although cigarette consumption is a reliable measure, it still does not accurately reflect actual tobacco (nicotine) exposure. Similarly, the number of years of education is a relatively accurate measure, but even if they are all in school, the years of education are the same, and everyone's academic achievements are also different. This problem still exists in Rietveld's research, which test index should be selected for research? It seems that we have indeed found some clues, but there is more work to be done later. The vague nature of the behavioral phenotype determines that this is destined to not be an easy task, and its difficulty is far more than finding genetic mutations related to smoking.

According to Rietveld's research, we can think that academic achievement and years of education may partially reflect a person's intelligence level, and those with high IQ usually do better in school. So is Rietveld's research the first case to successfully study the genetic basis of IQ? This will certainly cause a new round of debate.

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