Previous genetic association studies that involved individuals with European ancestry may have inaccurate results

A recent study conducted by the National Human Genome Research Institute (NHGRI) has revealed that previous genetic association studies involving people with European ancestry may have reported inaccurate results. The research suggests that failing to account for mixed genetic lineages could lead to misleading conclusions.

The researchers at NHGRI found that previous studies analyzing the genomes of individuals with European ancestry did not fully consider population structure. By considering mixed genetic lineages, the researchers demonstrated that previously inferred links between genomic variants and traits such as height, cholesterol levels, and lactose digestion may not be valid.

The study emphasizes the importance of adjusting for admixture in the population when evaluating data from genetic association studies of individuals with European ancestry. The researchers collated data from published genetic association studies and generated a reference panel of genomic data that included 19,000 individuals across 79 populations in Europe and European Americans in the US.

According to Daniel Shriner, a staff scientist at the NIH Center for Research on Genomics and Global Health and senior author of the study, analyzing the genetic makeup of Europe on a continental level is too simplistic. By considering admixture, true links between genomic variants and traits can be uncovered.

For instance, the researchers investigated the lactase gene, which plays a role in digesting lactose and is highly diverse 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 (bad cholesterol). The results showed that when considering the genetic admixture of the European population, the genomic variant related to lactose digestion is not linked to height or low-density lipoprotein cholesterol, but it does influence body mass index.

Charles Rotimi, NIH Distinguished Investigator and director of the Center for Research on Genomics and Global Health emphasizes the importance of accounting for complex ancestral backgrounds in genetic studies and genomic medicine. He states that appreciating the mixed ancestral backgrounds of individuals worldwide is crucial to avoiding false associations and uncovering true genetic links.

The study suggests that there may be other false associations in the literature and that some true associations are yet to be discovered. Understanding how genomic variants are related to different traits can help researchers estimate polygenic risk scores and provide insights into a person's ability to respond safely to drug treatments.

By accounting for mixed ancestries in future genomic analyses, researchers hope to improve the predictive value of polygenic risk scores and enhance the practice of genomic medicine. The reference panel generated in this study is available to the scientific community for use in additional studies, further advancing the understanding of genetic associations.