Genome-wide association studies (GWAS) provide an opportunity to associate concentration changes in certain proteins or metabolic products with gene loci. Knowledge of these genes makes it possible to establish connections to complex diseases. Scientists utilize the fact that to date, hundreds of associations between genetic variants and complex diseases have been demonstrated. These associations are immensely important because they do help uncover the underlying molecular mechanisms.
"In the world's largest proteomics GWAS to date, we worked with colleagues* to examine blood samples from 1,000 participants in the KORA study**," reports Dr. Gabi Kastenmüller. She is acting director and head of the Metabolomics Group at the Institute of Bioinformatics and Systems Biology (IBIS) at the Helmholtz Zentrum München. The team quantified a total of 1,100 proteins. Dr. Christian Gieger, head of the Molecular Epidemiology Research Unit (AME) at the Helmholtz Zentrum München, adds: "We found 539 independent associations between protein levels and genetic variants." These overlap with genetic risk variants for 42 complex conditions, such as cardiovascular diseases and Alzheimer's disease.
"Our results provide new insights into the biological processes that are influenced by a very wide range of complex diseases and that can be used as a basis for the development of new strategies to predict and prevent these diseases," Gieger states. The team is now planning to investigate the exact mechanisms behind the new gene-protein associations.
* Participants from the Helmholtz Zentrum München were: The Molecular Epidemiology Research Unit (AME), the Institute of Epidemiology 2 (EPI2), the Institute of Bioinformatics and Systems Biology (IBIS), and the Institute of Genetic Epidemiology (IGE). External partners were the German Center for Diabetes Research (DZD), the German Center for Cardiovascular Disease (DZHK), and Weill Cornell Medicine, Qatar and Doha, Qatar.
** KORA study: The "Kooperative Gesundheitsforschung in der Region Augsburg" (Cooperative Health Research in the Augsburg Region) study has been investigating the health of thousands of people living in the Greater Augsburg area for 30 years. The objective is to understand the effects of environmental factors, lifestyle and genes. Key topics of the KORA studies are issues involving the genesis and progress of chronic diseases, particularly cardiac infarction and diabetes mellitus. Risk factors from the area of health-related behaviour (such as smoking, nutrition, and physical activity), environmental factors (including air and noise pollution), and genetics are explored for this purpose. Issues regarding the utilization and costs of healthcare are examined from the point of view of healthcare research.
Karsten Suhre et al. (2017): Connecting genetic risk to disease endpoints through the human blood plasma proteome, Nature Communications, DOI: 10.1038/ncomms14357.