If you have ADHD, your chances are greater than your brothers. Estimates vary depending on how strong the connection is, but the arrows point to the same direction: genetics helps determine someone's risk for ADHD. Beyond that, we still have countless questions and not many answers – which genres play a role? And how do genes affect someone's ability to focus or stay still?
Some conditions, such as anemia of harvested cells, rely entirely on one small genetic change; but others, such as schizophrenia, are based on a staggering range of genetic differences, all apparently related to an infinitely small increase in risk.
ADHD is much closer to schizophrenia. A paper published in Nature Genetics this week analyzed genetic data from more than 50,000 people, finding 12 different DNA regions that seemed to play a role in increasing the risk of ADHD.
A vision at the genome level
This evidence comes from a genotyping study or GWAS: a careful look at how DNA of people with ADHD differs from those without. People can have slightly different versions of the same genre, with just one letter changed for another in a paragraph. If any of these variations modify a particular illness, you should find that people suffering from this condition tend to have more variants and people without the need for a different variant. So scanning the genome, those variants that appear to be different between the two groups deserve to be careful.
Because it has become easier to create and analyze data from larger samples, GWAS studies have examined the genome of tens of thousands – in some cases, hundreds of thousands. These huge numbers are needed for researchers to detect the minor differences that may be at stake. Smaller studies tend to appear empty or identify a handful of genetic regions that seem to play a role, while larger studies can pick up a huge number of variants.
Previous efforts to find variants related to ADHD have not highlighted anything, but could have been because they did not have sizes large enough for samples.
Geneticist Ditte Demontis and her colleagues used data from over 20,000 people with ADHD, comparing them with a control group of 35,000 people without ADHD diagnosis. They found 304 points, in which the tiny differences between single-letter type DNA swaps – were distributed in the two groups in a statistical way. If any of these variants were very close, the researchers considered them to be the same stretch of DNA, grouping them into 12 important regions.
There is no "gene for ADHD"
It is still unclear what information GWAS can provide us with. Extensive studies can identify many genes involved in a condition, each with little influence, causing a lot of debates on how to interpret them best. Some researchers even argue that in some cases what we see is essentially the entire genome that plays a role in a certain condition.
Combining all the small risks offered by different genetic variants can generate what is called a "polio risk score" – a way to capture how high a person's risk of having a condition is, based on the number of individual risky variants they have it. Even they have a limited applicability, though: "For schizophrenia, these scores can account for about five percent of the disease's variation," writes neurologist Kevin Mitchell.
In fact, the multitude of small increases in risk can tell us that the genes involved are not directly related to the condition. Instead, it could create a basic state in which a multitude of different genes will function in a slightly less ideal way, making it harder to "tampon the effects of rare mutations," writes Mitchell. There is also a significant overlap between the poligen risk scores for different conditions, suggesting that the genetic variation identified in the GWAS studies seems to leave vulnerable people to a number of different conditions.
This overlap is exactly what Demontis and her colleagues found with ADHD. There have been correlations between genetic risk for ADHD and a number of other conditions, including depression and anorexia. This is linked to the idea that genetic variation could be important in a way that would take place throughout the system. Some of the genes they have identified are also known to be involved in other neurological disorders, including speech and learning disabilities, depression and schizophrenia.
This research is light years away from anything that will immediately affect people with ADHD, such as a genetic test or a drug. But that does not make it useless. It's just creating routes for additional research, rather than practical application. Scientists will obviously want to look closely at these genes to study how they work in humans. But the most obvious next step is a much larger study: although this sample size seems great, a larger GWAS could identify even more genetic variants involved in ADHD, helping to clarify its overlaps with other conditions.
Nature Genetics, 2018. DOI: 10.1038 / s41588-018-0269-7 (About DOI).