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Large genetic study finds first genes connected with ADHD



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Large genetic study finds first genes connected with ADHD

If you have ADHD, chances are high that your siblings do, too. Estimates differ as to how strong the connection is, but the arrow is in the same direction: genetics helps determine someone's risk for ADHD. Beyond that, we still have myriad questions and not many answers-which genes play a role? And how do they affect someone's ability to focus or sit still?

Some conditions, like sickle-cell anemia, rest on a small genetic change; But other, like schizophrenia, rest on a dizzying array of genetic differences, all in the form of an infinitesimally small growth in risk.

ADHD is very close to schizophrenia A paper published in Nature Genetics This week looked at genetic data from 50,000 people, finding 12 different regions of DNA that seemed to play a role in ADHD risk.

A genome-wide view

This evidence comes from a genome-wide association study, or GWAS: a close look at how the DNA of people with ADHD differs from those without. People have slightly different versions of the same gene-like having just a single letter swapped out for a different one in a paragraph. If any of these variants make a difference to a particular disease, you should find that people with the condition tend to be more variant and people without the condition have a different one. So, scanning across the genome, those variants that pop up as being different

As it has become easy to create and analyze data from ever-larger sample sizes, GWAS has studied the genomes of ten thousand of people-in some cases hundreds of thousands. Those huge numbers are necessary for researchers to detect the small differences that can be at play. Smaller studies tend to come up or identify a handful of genetic regions that seem to play a role, while large studies can kick up huge numbers of variants.

Previous efforts to find ADHD-related variants had not turned up anything, but that did not have big enough sample sizes.

Geneticist Ditte Demontis and his 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-like single letter swaps-were distributed across their groups in a statistically telling way. If any of those variants were very close together, the researchers counted them as the same stretch of DNA, grouping them together in 12 important regions.

There is no "gene for ADHD"

It's not clear yet what information GWAS research can give us Large studies can identify many genes in a condition, each having a small influence, causing a lot of debate about how best to interpret them. Some researchers even argue that, in some cases, what we're seeing is an important condition.

Combining all the tiny risks conferred by different genetic variants can yield what is called a "polygenic risk score" – a condition for capturing how high a person's risk is, they have the different risky variants of the number based on them. Even these have limited applicability, though: "for schizophrenia, these scores can explain about five percent of the variance in disease status," neuroscientist Kevin Mitchell writes.

In fact, the multitude of tiny increases in risk may tell us that the genes involved are not directly related to the condition. Instead, they may be making an underlying state in which plenty of different genes end up functioning in a slightly less ideal way, making it harder to "buffer the effects of rare mutations," Mitchell writes. There is also significant overlap between the polygenic risk scores for different conditions, suggesting that the GWAS studies in identifying the genetic variation are different conditions of the population of the people.

That overlap is exactly what Demontis and his colleagues found with ADHD. There were correlations between the genetic risk for ADHD and a range of other conditions, including depression and anorexia. That ties in with the idea that genetic variation may be important in a way that plays out system-wide. Some of the genes they have identified are also involved in other neurological conditions, including speech and learning disabilities, depression, and schizophrenia.

This research is light-years away from anything that will affect people with ADHD-like a genetic test or a medicine. But that does not make it useless It's just making routes for additional research, rather than practical application. Scientists would obviously want to look at these genes But the most obvious next step is a much bigger study: although this sample size looks large, a bigger GWAS could also identify more in genetic variants of ADHD, helping to clarify its overlaps with other conditions.

Nature Genetics, 2018. DOI: 10.1038 / s41588-018-0269-7 (About DOIs).

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