A recent study conducted by researchers at the National Human Genome Research Institute (NHGRI) has raised concerns about the accuracy of previous genetic association studies involving individuals of European ancestry. The researchers have discovered that these studies may have produced inaccurate results due to a lack of consideration for the population’s genetic diversity, often referred to as admixture.
In the study, published in Nature Communications, the researchers demonstrated that individuals of European ancestry, who were previously treated as a genetically homogenous group in large-scale genetic studies, actually exhibit evidence of mixed genetic lineages. This means that the results from previous genome-wide association studies that did not account for admixture in their analyses should be re-evaluated.
Dr. Daniel Shriner, a staff scientist at the NIH Center for Research on Genomics and Global Health and the senior author of the study, emphasized the need to adjust for admixture in genetic association studies involving people of European ancestry. The researchers compiled data from published genetic association studies and created a reference panel of genomic data, encompassing 19,000 individuals from European ancestry across 79 different European populations and European Americans in the U.S. This allowed them to capture the ancestral diversity that was absent from other catalogs of human genomic variation.
As an illustrative example, the researchers examined the lactase gene, responsible for lactose digestion, which displays significant variability across Europe. Using their new reference panel, they investigated the link between a specific genomic variant of the lactase gene and traits such as height, body mass index, and low-density lipoprotein cholesterol (often referred to as “bad cholesterol”).
Upon accounting for the genetic admixture in the European population, the researchers found that the genomic variant responsible for lactose digestion is not associated with height or low-density lipoprotein cholesterol. However, it does influence body mass index. These findings underscore the importance of considering complex ancestral backgrounds in genetic studies and genomic medicine.
Dr. Charles Rotimi, director of the Center for Research on Genomics and Global Health and another senior author of the study, emphasized that most individuals worldwide have mixed ancestral backgrounds, and addressing these complexities is crucial for genetic studies. The study suggests that other false associations may exist in the literature, while some true associations remain undiscovered. Identifying genuine genetic associations is essential for improving the accuracy of polygenic risk scores and enhancing the practice of genomic medicine.
Though the genetic variation between any two individuals is relatively small (less than 1%), it can provide valuable insights into a person’s ancestral origins and genetic risks for common diseases. The researchers believe that accounting for mixed ancestries in future genomic analyses will enhance the predictive value of polygenic risk scores and facilitate advancements in genomic medicine.
The reference panel created during this study is made available to the scientific community for use in further research, as detailed in the published paper.
