European Ancestry: Inaccuracies Unveiled in Genetic Research by NIH

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Microscopic Examination of European Ancestry: Inaccuracies Unveiled in Genetic Research by the National Institutes of Health (NIH)

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Microscopic Examination of European Ancestry: Inaccuracies Unveiled in Genetic Research by the National Institutes of Health (NIH)

Researchers from the National Institutes of Health (NIH) in the United States have discovered that when studying the genetics of European populations, not accounting for mixed heritage can lead to erroneous associations between genetic variations and traits. Their findings call for a reevaluation of such studies, particularly in the context of the lactase gene’s impact on characteristics like height.

NIH Study Highlights the Impact of Neglecting Mixed Genealogy

Researchers found that previous genetic studies on European ancestry populations may have reported inaccurate results due to inadequate consideration of population structure. Scientists at the National Human Genome Research Institute (NHGRI), a branch of the NIH, demonstrated that previous assumptions regarding genetic variations contributing to lactose digestion and their relationship to traits like height and cholesterol levels may not be valid when mixed genetic lineages are factored in.

Gene Hybridization

Published in “Nature Communications” on November 7th, this study suggests that people of European descent, previously treated as a homogenous genetic group in large-scale genetic studies, exhibit clear evidence of mixed gene lineages, or what is commonly referred to as mixed heritage. Therefore, prior whole-genome association studies on people of European ancestry should be reconsidered as they did not account for mixed heritage when examining this population.

“By reviewing population genetics literature, we realized that the genetic makeup of Europeans is far too intricate to be observed at the continental level,” says Dr. Daniel Shriner, a Senior Author of the study and Staff Scientist at the NIH Center for Research on Genomics and Global Health. “According to our analysis, it’s evident that when evaluating genetic association study data in European ancestry populations, researchers should adjust for the presence of mixed heritage within the population to discover genuine links between genetic variations and traits.”

To investigate the genetic ancestors of Europeans, scientists compiled published genetic association research data and generated a reference panel of genetic data, including 79 European populations and 19,000 individuals of European ancestry in the United States. This allowed them to capture ancestral diversity not seen in other large human genome variation catalogs.

For example, the researchers examined the lactase gene, which encodes a protein aiding in lactose digestion and exhibits significant variations across different European regions. Utilizing the new reference panel, they analyzed the relationship between genetic variations in the lactase gene and traits such as height, body mass index, and low-density lipoprotein cholesterol (commonly known as “bad cholesterol”).

Taking gene hybridization among European populations into account, the researchers found that the genetic variants associated with lactose digestion capacity were unrelated to height or low-density lipoprotein cholesterol levels. However, the same variant did affect body mass index.

Implications for Genomic Research

Dr. Charles Rotimi, a Senior Author of the study and an NIH Distinguished Investigator, as well as the Director of the Center for Research on Genomics and Global Health, emphasized, “This study’s findings underscore the importance of recognizing that the majority of individuals within global populations have mixed ancestral backgrounds and that accounting for this complex ancestry is crucial in genetic research and genomic medical practices.”

The researchers note that the lactase gene is just one example of a gene that may have been incorrectly associated with certain traits in previous analyses. There are likely other erroneous associations in the literature, with some genuine associations yet to be discovered. Understanding the relationship between genetic variations and different traits provides important clues for researchers to estimate polygenic risk scores and gain insights into an individual’s ability to respond to medical treatments.

While the genetic differences between any two individuals account for less than 1% of the genome, this small portion of genetic variation can offer clues about an individual’s potential ancestral origins and relationships between different lineages. Information about one’s biological ancestry, often referred to as genetic ancestry, can provide important insights into genetic risk for common diseases.

Dr. Mateus Gouveia, the lead author of the study and a researcher at the Center for Research on Genomics and Global Health, states, “Identifying genuine genetic associations will help researchers conduct further studies more efficiently and cautiously. We hope that by considering mixed heritage in future genomic analyses, we can enhance the predictive value of polygenic risk scores and advance the field of genomic medicine.”

The reference panel produced in this study is available for use by the scientific community for further research, with more information provided in the paper.

Microscopic Examination of European Ancestry: Inaccuracies Unveiled in Genetic Research by the National Institutes of Health (NIH)

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