Researchers have found that previous studies analyzing the genomes of people with European ancestry may have reported inaccurate results by not fully accounting for population structure. Credit: Darryl Leja, National Human Genome Research Institute
Key points:
- A new study says the results from previous genome-wide association studies that do not account for admixture in their examinations of people with European ancestry.
- Information about who a person is biologically descended from can give important clues about genetic risks for common diseases.
- The NIH team suggests examinations of people with European ancestry should be re-evaluated.
Researchers have found that previous studies analyzing the genomes of people with European ancestry may have reported inaccurate results by not fully accounting for population structure.
The study by NIH researchers, published in Nature Communications, shows that people with European ancestry—who were previously treated as a genetically homogenous group in large-scale genetic studies—have clear evidence of mixed genetic lineages, known as admixture. As such, the results from previous genome-wide association studies that do not account for admixture in their examinations of people with European ancestry should be re-evaluated.
For the study, researchers collated data in published genetic association studies and generated a reference panel of genomic data that included 19,000 individuals of European ancestry across 79 populations in Europe and European Americans in the U.S., capturing ancestral diversity not seen in other large catalogs of human genomic variation.
This specific study focused on the lactase gene, which encodes a protein that helps digest lactose and is highly varied across Europe. Using the new reference panel, they analyzed how a genomic variant of the lactase gene is related to traits such as height, body mass index and low-density lipoprotein cholesterol, also known as bad cholesterol.
When the researchers considered the genetic admixture of the European population in their analysis, they found that the genomic variant that gives people the ability to digest lactose is not linked to height or level of low-density lipoprotein cholesterol. In contrast, the same variant does influence body mass index.
While the lactase gene is one example of a gene that may be incorrectly linked to some traits based on previous analyses, the researchers say it’s likely that there are other false associations in the literature and that some true associations are yet to be found.
“The findings of this study highlight the importance of appreciating that the majority of individuals in populations around the world have mixed ancestral backgrounds and that accounting for these complex ancestral backgrounds is critically important in genetic studies and the practice of genomic medicine,” said Charles Rotimi, NIH Distinguished Investigator, director of the Center for Research on Genomics and Global Health and senior author of the study.