Two Main Gene Discovery Methods Reveal Complementary Aspects of Biology

 


The two main approaches for discovering disease genes reveal distinct aspects of biology, a new study shows. Although both methods are widely used, the research found that they identify different genes, with major implications for drug development.

Published online November 5 in Nature, the study revolves around the human genome, which contains thousands of genes that provide instructions for making proteins, as well as regulatory DNA that controls when genes turn on. The new investigation takes a genome-wide view of how small DNA differences—called variants—can influence traits such as height, hair color, and disease risk.

Led by researchers at NYU Langone Health; Stanford University; University of California, San Francisco; and the University of Tokyo, the new work analyzed two main methods used to determine how genetic differences influence disease biology. These are genome-wide association studies (GWAS), which test common variants across the genome—in genes and regulatory regions—to find those linked to disease, and burden tests, which focus on rare variants that alter proteins.

By analyzing GWAS and burden test results for 209 traits from the UK Biobank, which contains genetic data from hundreds of thousands of people, the researchers found that burden tests identify genes that mostly affect the disease being studied, with little effect on other traits, while GWAS can identify both these disease-specific genes and genes that influence many diseases and biological processes.

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