Genomic Risk
A major goal of the eMERGE network is to develop and return genomic risk assessments to participants and their clinicians. Genomic risk assessments (GRAs) are designed to help predict the onset of diseases that have a substantial heritable component, such as certain cancers or cardiac conditions. Determining why some individuals are prone to these conditions can help physicians tailor screening strategies, enable early diagnosis, or implement preventative care that delays or averts disease onset. While the etiology of disease is complex, recent scientific discoveries have identified large networks of genes (polygenic risk) associated with disease onset and distinct from the well described single gene (monogenic) risks. These genomic risks are rarely deterministic and influenced by one’s personal health history, environment, family history, health behavior and other important determinants such as access to health care. Integrating these different risk factors into a single assessment is a major focus of eMERGE network. Below are explanations of each type of risk factor, and how they contribute to the overall risk of developing a given condition.
Monogenic determinants
Monogenic diseases (also known as Mendelian disorders) are a result of alterations to a single gene. Some commonly known monogenic diseases are cystic fibrosis and sickle cell anemia. Other monogenic variants are strongly associated with cancers, cardiomyopathies, familial hyperlipidemia and other disorders. During a previous phase of the eMERGE network (more information here), we examined how monogenic pathogenic variants in genes associated with conditions like Hereditary Breast and Ovarian Cancer, Lynch Syndrome, and Familial Hypercholesterolemia, known as Tier 1 conditions. The network is currently determining how risk of monogenic disease integrates with other risk factors like polygenic and family history to determine how overall genomic risk contributes to disease development and progression.
Polygenic determinants
Polygenic risk is defined when many genes or variations in gene across your genome contribute to the development of a disease. Each individual gene variant has a small contribution to the overall risk and are often combined together into a risk score. Learn more about polygenic risk on the NHGRI website and the Broad Institute.
Family History
Family history plays an important role in the development of disease, as families share genes, environments, and lifestyle. Studies have shown that family history is independently predictive of disease even after accounting for known genetic risks. More information is available on the NIH website. The eMERGE Network is utilizing the MeTree tool, developed by Duke University, to capture family health history and integrate with other risk factors to examine overall genomic risk.
Clinical determinants
Clinical risk factors include demographics (age, sex, self-reported race), biometrics (body-mass index), comorbidities (hypertension), laboratory values (cholesterol, glucose) and key health behaviors (smoking and alcohol use) measured clinically and available at the point of care to estimate risk of disease. By taking into consideration a person’s clinical risk factors, the network can leverage existing, validated risk models to better understand a person’s overall risk of developing a given condition.
Social Determinants
Social determinants of health (SDOH) are how the environment a person lives in, grows up in, works in, and interacts with that can have influences on their health and outcomes of diseases. Five major SDOH include Economic stability, Education access & quality, Health care access & quality, Neighborhood & environment, and Social & community interactions. Learn more about SDOH on the Healthy.gov and World Health Organization websites.