European Genetic Variants are Poor Predictors of Disease in the Middle East

2021-03-18

European genetic studies aren’t particularly accurate when applied to Middle East populations, according to new research from the Qatar Foundation. The first large whole genome sequencing study of the Qatari population, published in Nature Communications, is the first study to identify genetic variations that are specific to the Qatari population. It also provides new insights into the genetic architecture of clinical laboratory tests. “In this study, we found that genetic variations that control many lab tests (mainly related to blood cells) that were identified from studies of European populations have lower predictive performance when applied to the Qatari populations (i.e., they don’t translate well to Qatar),” Omar Albagha, Ph.D., joint senior author of the paper and professor of genomic and precision medicine at Hamad Bin Khalifa University’s College of Health and Life Sciences, told BioSpace. That said, the study noted that trait heritability is more similar between Qatari and European populations than between Qatari and African or Japanese populations. The research, Albagha said, “focused on blood lab tests, which are routinely used to assess patients and follow their treatments, because we know that genetic factors contribute to lab test measurements. “Therefore, to develop precision medicine, we need more studies to identify the collection of genetic variations that best predict diseases in the Middle Eastern populations. We cannot simply take the findings from European populations and directly apply them to the Middle East, because the genetic architecture of diseases varies with populations,” he said. This research assessed the genetic variants across the whole genome across 6,128 individuals and was confirmed against a screening of samples from 7,768 individuals from the Qatar Biobank. “The study was based mainly on Qataris and long-term residents from the Middle East,” he added. By exploring the data from 45 clinically relevant traits, Albagha and colleagues identified “281 distinct variant-trait-associations at genome-wide significance that replicate known associations,” the paper noted. Of those, 17 were found predominantly in Qataris. Notable heritability differences included height, body mass, cholesterol, red blood count and white blood count, among others. When the predictive performance of polygenic scores (PGS) from 11 traits was tested on data from the Qatar Genome Project (QGP), “all tested PGS showed lower performance when applied to QGP data, with an average performance of 64.7% of that when applied to Europeans,” the paper noted. The predictive differences may result from environmental or lifestyle factors, the study suggested, citing cholesterol as an example. The estimates for TCH and LDL-C are significantly lower than values reported in European or African populations, “suggesting a higher contribution of environmental influences, such as diet and lifestyle.” Body mass index heritability estimates were also lower, the authors wrote, noting that obesity in Qatar is among the highest in the world. Linkage disequilibrium patterns among populations appear to play a role in the predictive differences. Analysis showed “marked differences in linkage disequilibrium and allele frequencies among the European, East Asian, and Qatari populations.” The results of this study may be applied to the entire Middle East. “The results apply to individuals who share common family roots that may go back a few hundred years or more – so they certainly apply to people living in the Middle East North Africa (MENA) region, and probably also to most of the Arab populations in the Middle East,” Karsten Suhre, Ph.D., joint senior author on the paper and director of bioinformatics core at Weill Cornell Medicine – Qatar, told BioSpace. “Further studies from other Arab populations are needed to obtain a more detailed picture.” “To the best of our knowledge, there is no published study describing genomic data of a similar size from the Middle East,” Albagha said. “Most published studies are based on a small size and are focused on a few lab tests of a single disease.” Suhre added, “The next largest study we know of also was conducted by us, with 996 participants from Qatar.” It used more general biochemical readouts rather than clinically relevant traits. “The findings of this study have been deposited in a publicly accessible database for researchers around the world. When our findings are combined with those from other populations, it is possible to identify additional genetic variations – especially if these variations are rare in other populations, such as Europeans, but common in Qataris,” Albagha said. In light of these findings, it is important to consider the specifics of the Arab genome as new therapies are developed. “These new variations could be useful targets for designing new treatments,” he said.

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