Researchers at the National Human Genome Research Institute (NHGRI) have revealed that not properly considering mixed ancestries in genetic research concerning European populations could lead to false associations of genetic variants with physical traits. They particularly emphasize the need to reassess past studies, especially those relating to the influence of the lactase gene on characteristics like height.
An NIH investigation suggests that overlooking mixed genetic ancestries may result in research inaccuracies.
It has been uncovered that prior genetic analyses of European descent might have concluded with erroneous outcomes due to the inadequate inclusion of diverse population structures. NHGRI experts, associated with the National Institutes of Health (NIH), discovered that presumed correlations between genetic variants aiding in lactose digestion and traits such as stature and cholesterol levels might be invalid upon considering mixed ancestries.
Genetic Mixture Considerations
The research, released today (November 7) in Nature Communications, indicates that individuals with European backgrounds, who have been historically perceived as genetically uniform in extensive genetic studies, actually present a significant mixture of genetic ancestries, referred to as admixture. This finding suggests that former genome-wide association studies that did not account for admixture when examining European individuals might need to be reassessed.
The researchers discovered that previous investigations into the genomes of Europeans might have relayed imprecise findings by not thoroughly considering population structures. Credit goes to Darryl Leja from the National Human Genome Research Institute for this insight.
Research Outcomes
“Our scrutiny into population genetics literature showed that Europe’s genetic composition is too intricate for a broad continental overview,” mentioned Daniel Shriner, Ph.D., staff scientist at the NIH Center for Research on Genomics and Global Health and the study’s lead author. “Our analysis confirms the necessity of adjusting for admixture when assessing genetic association study data from European descendants to discern accurate relationships between genetic variants and characteristics.”
To delve into European genetic heritage, the team assembled data from various genetic association studies and created a comprehensive genomic data reference panel. This panel includes data from 19,000 individuals of European descent, encompassing 79 populations within Europe and European Americans in the U.S., highlighting ancestral variety not observed in other comprehensive human genomic variation catalogs.
For instance, the team studied the lactase gene, responsible for lactose digestion and notably diverse across Europe. Employing the newly established reference panel, they examined the relationship between a variant of the lactase gene and traits like height, body mass index, and low-density lipoprotein cholesterol, also known as “bad cholesterol.”
The analysis, taking into account the European population’s genetic admixture, showed that the lactase gene variant enabling lactose digestion does not correlate with height or bad cholesterol levels. Conversely, it does affect body mass index.
Consequences for Genomic Studies
“The insights from our study underscore the critical nature of recognizing mixed ancestral backgrounds in most global populations and the importance of considering these complexities in genetic research and genomic medicine practices,” stated Charles Rotimi, Ph.D., the NIH Distinguished Investigator, director of the Center for Research on Genomics and Global Health and the study’s senior author.
Although the lactase gene serves as just one instance of potential misassociations, the researchers suggest there might be other incorrect links in the literature and undiscovered true associations. Understanding how genomic variants relate to traits assists researchers in determining polygenic risk scores and could provide indicators of an individual’s compatibility with certain medications.
While only a minor fraction under 1% distinguishes any two human genomes, these slight variations can offer insights into a person’s ancestral origins and familial connections. This genetic lineage can reveal critical information about hereditary risks for common diseases.
“Identifying accurate genetic associations will refine the research approach, fostering more meticulous and efficient future investigations,” asserted Mateus Gouveia, Ph.D., research fellow at the Center for Research on Genomics and Global Health and the study’s principal author. “We anticipate that by incorporating mixed ancestries into forthcoming genomic analyses, we can enhance the predictive accuracy of polygenic risk scores and aid genomic medicine.”
The reference panel created through this study is now accessible to the research community for further study, with additional details provided in the publication.
Reference: “Overlooked Subcontinental Admixture in Europeans and European Americans: Consequences for Genetic Epidemiology Research” 7 November 2023, Nature Communications.
DOI: 10.1038/s41467-023-42491-0
Table of Contents
Frequently Asked Questions (FAQs) about genetic ancestry admixture
What does the NHGRI study on European genetic ancestry reveal?
The study exposes inaccuracies in previous genetic research that failed to consider the mixed ancestries in European populations, leading to false associations between genetic variants and traits like height and cholesterol levels.
Why is accounting for admixture important in genetic studies?
Accounting for admixture is crucial to avoid incorrect correlations in genetic research. Mixed ancestries provide a more accurate representation of population structures, which is essential for identifying true links between genes and traits.
What are the implications of this study for future genetic research?
This research implies that future genetic studies should incorporate admixture to improve the accuracy of associations between genomic variants and traits. This is important for the development of polygenic risk scores and for advancing personalized medicine.
How was the NHGRI study conducted?
The study was conducted by creating a reference panel from data of 19,000 individuals across 79 populations, which included a mix of European and European American ancestries. This helped to analyze the impact of admixture on trait associations.
What was the role of the lactase gene in the NHGRI study?
The lactase gene was investigated to determine its relation to certain traits. The study found that when admixture is considered, the ability to digest lactose, associated with the gene, does not affect height or bad cholesterol levels but does influence body mass index.
More about genetic ancestry admixture
- Nature Communications Journal Article
- National Human Genome Research Institute (NHGRI)
- NIH Genomics and Global Health
- Genetic Admixture Research
- Polygenic Risk Scores Overview
