In a Finnish study that included UCLA researchers, the DNA of nearly 20,000 people was exploited to identify genetic mutations that could increase the risk of diabetes, high cholesterol and other diseases and conditions.
The discoveries, published in the journal Nature, suggests the potential for the use of genomic sequencing to uncover variations that can increase the risk of numerous common health problems, including heart disease, obesity and metabolic syndrome. Researchers have also identified genetic differences that can result in lower-than-average height and weight.
The authors of the study – coming from UCLA, the University of Washington, University of Michigan, University of Helsinki in Finland and 18 other institutions – stated that they found 26 variations potentially harmful genetics. Nineteen of these variations are unique or 20 times more likely in the Finnish population examined for the study.
Author of the Dr. Nelson Freimer, Maggie G. Gilbert Professor of Psychiatry and Human Genetics and Director of the Center for Neurobehavioral Genetics at Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, led the research with Michael Boehnke, professor of biostatistics at Richard G. Cornell Distinguished University and director of the Center for Statistical Genetics at the School of Public Health of the University of Michigan. Freimer discussed the meaning of the study.
Would you describe the idea for the study and why was Finland chosen as a study site?
In recent years it has become evident that if we want to identify the genetic variations that contribute to common diseases or common traits, we will need to sequence the genomes of a large number of people. And this is an idea that has become accessible to be realized only in recent years.
It has also become clear that what we have thought of as really great studies may not be large enough to find these genetic variations. Populations, such as those in northern and eastern Finland, have grown in isolation in recent centuries so as to be much more homogeneous than populations in the United States or in the larger European countries, where genetic variations such as these are rather rare.
The study was conceived as one that would measure the effectiveness of sequencing the specific genome to discover these genetic variants that can lead to diseases and common traits. As with other countries in the Nordic region, Finland has invested many resources in studies to evaluate the different traits of populations like this. So the data on the section we needed was already there.
Are people in northern and eastern Finland more prone to certain ailments or diseases?
Finnish hereditary disease it is a genetic disease that is significantly more common in Finnish people. It includes 36 rare diseases, including those not common in larger and different populations.
Furthermore, our study found dozens of new associations to genetic variations related to specific traits. And we know that based on what those variations do, they could be harmful and have the potential to cause disease. These variations would never have been associated with those traits in more diverse populations, because they would have been so rare and more difficult to find. So what we see is that these genetic variations are anywhere from 10 times to infinitely more frequent in Finland than in other populations.
What was learned from the study?
We learned that sequencing – not the entire genome but genes within the genome – is more convenient than sequencing the entire genome and just as reliable for finding variations that have a pretty strong effect on traits common as height, weight and cholesterol level.
We have found that the strategy of sequencing large samples of people to find genetic variants that influence the disease will work. But in populations like that of the United States or in large European countries like the United Kingdom, it will take sequencing, not of 20,000 people, but of several hundred thousand millions of people before getting the same kind of discovery.
How do the results translate into a more diverse population?
The United States launched a precision medicine effort, called All of us, which ultimately intends to sequence more than 1 million people. But even in large and diverse populations, as in the United States, there are people in some regions that do not move as much as people in other regions. And, in those populations, you might end up seeing genetic variations that are more clustered, like the ones we see in Finland. This suggests to me that precision medicine will have to take into account these regional differences. You can't expect a kind of precision medicine to work for an entire country.
What is the takeaway message of this study?
There are some people who ask, "Should we really devote resources to sequencing large human populations?" And I think the study shows us that it's worth investing.
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