New Research Shows Genetic Discoveries Apply Across Human Populations

Research over the last ten years has shown that alongside lifestyle factors, genetic information can help predict many traits - from height, to metabolic rate, cholesterol level, and disease. Studies have linked tens of thousands of mutations to predict a huge variety of traits. “However, a major challenge and controversy is that the largest studies are conducted in people of European ancestry, and our best genetic predictions for people of other ancestries are less accurate”, said Dr Sile Hu of Oxford University, who led the study.

Dr Daniel Lawson of Bristol University said: “This study tries to understand this inequality. We wanted to see if the data supports a difference in biology between populations, or if the problem is just a lack on knowledge”. Under the first theory, a mutation’s effect simply differ between groups, either because it depends on the environment (e.g. lifestyle), or the rest of the genome. The second theory is based on the fact that most mutations identified as important in genetic studies are not the ones that actually impact the trait, but are a nearby proxy for the true causal mutation. Being a good proxy in Europeans does not guarantee they will be a good proxy within a different ancestry. 

To determine which of the two issues above is driving this discrepancy, the scientists leveraged data from the UK Biobank, a study which has mapped variation and measured traits in almost half a million people. They first developed methods with the resolution to tell apart people from adjacent UK counties. They then applied these to compare traits, and genetic predictions of those traits, in people of different ancestries within the study. Prof Garrett Hellenthal of University College London said: “By leveraging the fact that many people in the study possess mixtures of different ancestries, we were able to show that a person’s ancestry typically does not influence the effect of a mutation, largely ruling out the first possibility.” Across the 53 traits studied, the effect sizes in African and European ancestry were estimated to be 98% correlated. For a few unusual traits, including white blood cell count, there is evidence that mutations may have different effects in different groups. In the future, it will be important to further examine these, and other, traits, by conducting diverse studies that sample individuals from many countries and ancestry backgrounds. 

Prof Simon Myers of Oxford University concluded: “One implication of the study is that where genetic studies identify the correct mutation that affects a trait, the underlying biology is typically the same in all people.” However, the study reinforces that studying only one population may lead to identifying the wrong mutation. Instead, leveraging studies incorporating people of diverse ancestries can better capture the true mutations impacting a trait. This will improve genetic predictions of traits for all humans,  regardless of their ancestry.

This work was funded in part by a Wellcome Trust Collaborative Award.

Image: shows people of mixed ancestry carrying genetic markers nearby a genetic mutation affecting a trait

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