In a recent study, published in the open-access journal PLoS Genetics, an international team of researchers provide the first genetic dissection of the population structure of European Americans, focusing on identifying the contributions from different genetic ancestries that are important for disease gene mapping.
This is a timely issue as the last year has seen a dramatic upswing in genetic association studies and the discovery of almost a hundred new risk factors for common genetic diseases such as cancer and diabetes. If the subtle population substructure that exists within European American populations is not understood and accounted for, genetic association studies can produce incorrect findings if disease cases are compared to healthy controls that on average have different ancestry.
By systematically examining data from four actual disease association studies in European Americans, this study describes and characterizes the majority of population substructure in European Americans that could lead to spurious associations. “Although our work is far from a complete description of European American population history, for the purpose of disease gene mapping studies it is adequate to measure how closely each person’s genetic ancestry resembles three populations that can be roughly described as northwest European, southeast European, or Ashkenazi Jewish,” says Dr. David Reich, one of the senior authors on the study, an Associate Professor of Genetics at Harvard Medical School and an Associate Member at the Broad Institute of Harvard and MIT. “With this approach, we can avoid most false-positive associations due to population substructure in European American disease gene mapping studies. Our previous work has addressed related challenges in studies of African Americans and Latino Americans.”
Based on their discovery that ancestry from only three populations accounts for most of the potentially problematic substructure in European American disease association studies, the researchers scoured through published data sets to identify places in the genome where common DNA sequence variants differ substantially in frequency among these three ancestral populations and are therefore potentially informative for estimating genetic ancestry. The investigators then confirmed the utility of these genetic variants by testing them in DNA samples that their coauthors collected from the United Kingdom, Sweden, Poland, Spain, Italy, Greece and U.S. Ashkenazi Jews. “We identified 300 common genetic variants that have unusually different frequencies in the three ancestral populations: they are about 10 times more informative for predicting the ancestry of European Americans than random genetic variants”, says lead author Dr. Alkes Price, a post-doctoral researcher at the Harvard Medical School Department of Genetics and the Broad Institute of Harvard and MIT. “We can thus correct for population substructure in European American disease association studies using just these 300 markers.”
This panel of 300 markers should be valuable in targeted associated studies that follow up previously implicated candidate genes: by comparing the ancestry of disease cases to healthy controls using data from the panel of 300 markers, researchers can determine whether observed associations are genuine, and not false-positives due to population structure. The panel can also be used to match the ancestry of cases and controls prior to more comprehensive studies.
While the technology should provide a new tool in disease gene mapping studies, the researchers caution that the ability to roughly categorize individuals into populations with a small number of genetic markers is not useful in a clinical setting, nor does it completely eliminate the utility of self-described ethnicity. “Although these 300 markers give a reasonable estimate of the major components of genetic ancestry in European Americans, self-described ethnicity can still reflect environmental, social and cultural factors that may not be captured by estimating genetic ancestry,” says Dr. Joel Hirschhorn, one of the senior authors of the study, an Associate Professor of Genetics at Children's Hospital Boston and Harvard Medical School, and a Senior Associate Member at the Broad Institute of Harvard and MIT, “Because the genetic differences between these populations are very small, the study is most important for helping in gene discovery efforts, which will lead to better understanding of human biology in health and disease, and hopefully improved care for all patients over the long term.”
Andrew Hyde | alfa
Drug discovery: First rational strategy to find molecular glue degraders
03.08.2020 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
Chlamydia: Greedy for Glutamine
03.08.2020 | Julius-Maximilians-Universität Würzburg
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
Although no life has been detected on the Martian surface, a new study from astrophysicist and research scientist at the Center for Space Science at NYU Abu...
New approach creates synthetic layered magnets with unprecedented level of control over their magnetic properties
The magnetic properties of a chromium halide can be tuned by manipulating the non-magnetic atoms in the material, a team, led by Boston College researchers,...
Scientists of Tomsk Polytechnic University jointly with a team of the V.E. Zuev Institute of Atmospheric Optics of the Siberian Branch of the Russian Academy of Sciences have discovered a method to increase the operation range of optical traps also known
Optical tweezers are a device which uses a laser beam to move micron-sized objects such as living cells, proteins, and molecules. In 2018, the American...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
03.08.2020 | Information Technology
03.08.2020 | Information Technology
03.08.2020 | Life Sciences