Diagnosis versus Increased Risk

Diseases can be put into two categories based on the influence of genes: Mendelian diseases or complex diseases. Mendelian diseases, also called single gene disorders, are caused by a variant in a single gene in our DNA code. Alternatively, complex diseases are caused by many genetic variants in many genes, in addition to non-genetic factors, including lifestyle and environment. Having one or more genetic variants associated with a complex disease like colon cancer does not diagnose colon cancer, but rather, may increase one's risk for the disease.

Mendelian Diseases

Some Mendelian diseases occur if you have inherited just one mutated copy of a gene from either your mother or your father. These diseases are called dominant disorders.

diagnosis versus risk chartHuntington's disease (HD) is an example of a dominant Mendelian disease. Huntington's disease is a neurodegenerative disorder that affects brain function and muscle movement. A person develops HD if they inherit one mutated copy of the Huntington's disease gene (called the HTT gene) from their mother or father. The mutation in the HTT gene is a copy number variant (CNV), meaning that the mutated copy contains a codon, or three letter word, that repeats in the genetic code.

Other Mendelian diseases will not develop unless you inherit two copies of a mutated gene (one from your mother AND one from your father). These diseases are called recessive disorders. Individuals who have only one mutated copy of the gene are called carriers. Carriers can pass the mutated copy of the gene to their children but won't be affected with the disease themselves.

Cystic fibrosis (CF) is an example of a recessive Mendelian disease. This disease affects a person's ability to transport chloride throughout their body, which causes problems with the lungs, pancreas, and small intestines. This chloride transportation issue results in a buildup of a thick, sticky mucous in the lungs and other organs, making it difficult to breathe and digest food. A person develops CF if they inherit two mutated copies of the CFTR gene—one from their mother and one from their father. If a person inherits one normal copy of the CFTR gene, and one mutated copy, that person will not be affected with CF but will be a carrier.

Complex Diseases

complex disease chartUnlike Mendelian diseases, complex diseases do NOT have a single cause. While genetic variants can factor into your chance for developing a disease, non-genetic factors (like diet, exercise, and your environment) combine with your genes to influence what health conditions you may develop over your lifetime. It is the interaction between your genes, environment and lifestyle that ultimately causes complex diseases to occur. Examples of complex diseases are cancer, heart disease, and diabetes.

For coronary artery disease, approximately 49% of the risk is due to genetic factors, while the remaining 51% of the risk is due to non-genetic risk factors, like smoking, diet and exercise. The colored balls in the image below each represent a different genetic variant that has been found to be associated with an increased risk of coronary artery disease. Each of these genetic variants, along with many others, both known and unknown, contribute to the 49% estimated risk of coronary artery disease due to genetic factors. Because not all variants have been identified and because scientists are not certain of how multiple genetic variants interact with one another, it is difficult to estimate the amount that each variant contributes toward the 49% risk.