Mixed ancestry genetic research shows that little Native American DNA could reduce risk of Alzheimer’s disease

Genome-wide association studies

In 2005, researchers first used a revolutionary method called the genome-wide association study. Studies like this comb through huge sets of genome data and medical histories to see if people with certain diseases tend to share the same version of DNA – called a genetic marker – in specific places.

Thanks to this approach, researchers have identified many genes involved in Alzheimer’s disease. But this method can only find genetic markers for diseases that are common in the genomes of study participants. If, for example, 90% of participants in an Alzheimer’s disease study have European ancestry and 10% have Asian ancestry, a genome-wide association study is unlikely to detect risks. genetics for Alzheimer’s disease that are only present in people of Asian descent. .

The genetics of all people reflect the origin of their ancestors. But ancestry manifests itself in both genetic variation and social and cultural experiences. All of these factors can influence the risk of certain diseases, which can create problems. When social disparities in the prevalence of disease appear between racial groups, genetic markers of ancestry can be confused with genetic markers of disease.

African Americans, for example, are up to twice as likely as white Americans to develop Alzheimer’s disease. Research shows that much of this disparity is likely due to structural racism causing differences in nutrition, socioeconomic status, and other social risk factors. A genome-wide association study looking for genes associated with Alzheimer’s disease could confuse genetic variations associated with African ancestry with the genetic causes of the disease.

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While researchers can use a number of statistical methods to avoid such errors, these methods can miss important results because they are often unable to overcome the general lack of diversity in genetic data sets.

Leveraging genetics of mixed ancestry

Unraveling disparities in race, ancestry, and health can be a challenge in genome-wide association studies. Mixture mapping, on the other hand, is able to make better use of even relatively small datasets of underrepresented people. This method derives its power specifically from the study of people of mixed ancestry.

Mixture mapping relies on a quirk of human genetics – you inherit DNA in pieces, not in a homogeneous mixture. So if you have ancestors from different parts of the world, your genome is made up of pieces of DNA from different ancestry. This process of fragmented inheritance is called mixing.

Imagine the color code of a genome by ancestry. A person who has mixed European, Native American, and African ancestors may have striped chromosomes that alternate between green, blue, and red, with each color representing a certain region. A different person with similar ancestry would also have a genome of green, blue, and red chunks, but the order and size of the stripes would be different.

Even two biological siblings will have locations in their genome where their DNA comes from different ancestry. These ancestry bands allow companies like Ancestry.com and 23andMe to generate ancestry reports.

Since genome-wide association studies have to compare a large number of tiny individual genetic markers, it is much more difficult to find rare genetic markers for a disease. In contrast, mix mapping tests whether the color of a certain piece of ancestry is associated with disease risk.

The statistics are quite complicated, but essentially, because there are a smaller number of much larger ancestral chunks, it is easier to separate the signal from the noise. Mixture mapping is more sensitive, but it sacrifices specificity, as it cannot indicate the individual genetic marker associated with disease risk.

Another important aspect of mix mapping is that it examines individuals of mixed ancestry. Since two people with similar socio-economic experiences may have different ancestors in certain parts of their genome, mapping the mixtures can examine the association between this piece of ancestry and disease without confusing the social causes of the disease. with genetic causes.

Mapping of mixtures and Alzheimer’s disease

Researchers estimate that 58-79% of the risk of Alzheimer’s disease is caused by a genetic difference, but only about a third of these genetic differences have been discovered. Few studies have looked for genetic links with Alzheimer’s risk in people of mixed ancestry.

Our team applied mix mapping to a genetic dataset of Hispanic Caribbean people who have a mix of European, Native American, and African ancestry. We found a part of the genome where Native American ancestry made people less likely to have Alzheimer’s disease. Basically, we’ve found that if you have the color blue in that certain part of your genome, you’re less likely to develop Alzheimer’s disease. We believe that with further research we can find the specific gene responsible in the blue piece and have already identified possible candidates.

An important note is that the genetic diversity that plays a role in the risk of disease is not visible to the naked eye. Anyone of Native American ancestry at that particular place in the genome – and not just someone who identifies or looks like Native American – may benefit from some protection against Alzheimer’s disease.

Our article shows that to better understand the risk of Alzheimer’s disease, one needs to use methods that can better utilize the limited data sets that exist for people of non-European descent. There is still a lot to learn about Alzheimer’s disease, but each new gene linked to this disease is a step towards a better understanding of its causes and the search for potential treatments.

This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Diane Xue, Washington University and Hanley Kingston, Washington University.

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Diane Xue receives funding from NIA T32AG052354 Neurobehavior, Neuropathology, and Risk Factors in Alzheimer’s Disease Training Grant administered by the University of Washington

Hanley Kingston Receives Funding from University of Washington Undergraduate Research Training Grant T32GM081062