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If you have ADHD, chances are also higher than your siblings. The estimates differ as to the strength of the connection, but the arrows go in the same direction: Genetics helps determine a person's risk of ADHD. Beyond that, we still have a myriad of questions and few answers: which genes play a role? And how do these genes affect one's ability to focus or stay still?
Some diseases, such as sickle cell disease, rely entirely on a single small genetic change. but others, like schizophrenia, are based on a vertiginous number of genetic differences, all apparently related to an infinitely small increase in risk.
ADHD is much closer to schizophrenia. An article published in Nature Genetics This week, we examined genetic data from more than 50,000 people and discovered 12 different DNA regions that seemed to play a role in increasing the risk of ADHD.
A genome-wide view
This evidence comes from a genome-wide association study, or GWAS: it examines how the DNA of people with ADHD differs from that of unaffected people. People may have slightly different versions of the same gene, for example, a single letter exchanged for another in a paragraph. If one of these variants makes the difference for a particular disease, you should find that people with the disease tend to be more likely to have a variant and the unaffected ones have it. a different one. It is therefore important to pay attention to variants that appear different between the two groups.
As it has become easier to create and analyze data from larger and larger samples, GWAS studies have examined the genome of tens of thousands of people, even hundreds of thousands of people. These huge numbers are needed by researchers to detect the small differences that may be at play. Small studies tend to be empty or to identify a handful of genetic regions that seem to play a role, whereas large studies can give rise to a large number of variants.
Previous efforts to find variants related to ADHD had not succeeded, but that could have been due to the fact that they did not have enough samples.
The geneticist Ditte Demontis and her colleagues used data from more than 20,000 people with ADHD, comparing them to a control group of 35,000 people without an ADHD diagnosis. They found 304 points where tiny differences in DNA – such as single letter exchanges – were split between their two groups in a statistically revealing way. If one of these variants was very close to each other, the researchers considered them to represent the same segment of DNA, grouping them in 12 important regions.
There is no "ADHD gene"
The information that GWAS research can provide us is not yet clear. Large studies can identify many genes involved in a disease, each having a tiny influence, which causes much debate on the best way to interpret them. Some researchers even argue that in some cases we find that the entire genome plays a role in a given condition.
The combination of all the minimal risks conferred by different genetic variants can generate what is called a "polygenic risk score" – a way to determine a person's high risk for a disease, depending on the number of individual risk variants at its disposal. Even these have limited applicability, however: "For schizophrenia, these scores may explain about 5% of the variance in the state of the disease," writes neuroscientist Kevin Mitchell.
In fact, the multitude of small increases in risk could tell us that the genes involved are not directly related to the disease. Instead, they could create an underlying state in which a multitude of different genes end up functioning in a slightly less than ideal way, making it more difficult to "protect against the effects of rare mutations" , writes Mitchell. There is also significant overlap of polygenic risk scores for different conditions, suggesting that the genetic variation identified in the GWAS studies appears to make individuals vulnerable to a range of different conditions.
This overlap is precisely what Demontis and his colleagues discovered with ADHD. There were correlations between the genetic risk of ADHD and a range of other conditions, including depression and anorexia. This is consistent with the idea that genetic variation could be important in order to apply it to the whole system. Some of the genes that they have identified are also known to be involved in other neurological conditions, including speech and learning disorders, depression and schizophrenia.
This research is light years away from anything that will immediately affect people with ADHD, such as a genetic test or medication. But that does not make it useless. It's simply about creating routes for additional research, rather than practical applications. Scientists will obviously want to look closely at these genes to study how they work in humans. The next most obvious step is a much larger study: although the size of this sample may seem important, a larger GWAS could identify even more genetic variants involved in ADHD, which would clarify its overlap with other drugs. other conditions.
Nature Genetics, 2018. DOI: 10.1038 / s41588-018-0269-7 (About the DOIs).
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