The Role of Genetics in Multifactorial Disorders

Diseases are all different, and they don’t happen through their own specific mechanisms. Some diseases are classified as genetic disorders which are inherited solely through your DNA, while other diseases happen as a consequence of many different factors.

Preventing diseases largely depends on how they develop. Fortunately, genomics is a powerful tool that can provide helpful information to assess your past, present, and future health. As a result, you will be able to engage in different strategies to avoid disease.

But in order to achieve this, we need to understand the difference between single gene disease and multifactorial disorders. 

What are single gene disorders?

Single gene disorders, also known as monogenic disorders, are caused by a variant, or mutation, in a single genetic location. There can be different types of variants that result in the same disease, but with varying degrees of severity.

On their own, each single gene disorder is relatively rare. But as a whole, it has been estimated that this group of diseases affects approximately 1% of the total world population1 — which is around 75 million people around the globe.

We inherit two copies of each gene, one from each of our parents. The traits that are inherited through our genes can be either dominant or recessive.2 Dominant traits show up when a variant is present in a single copy of the gene, whereas recessive traits will only be expressed if you inherit two copies of the faulty gene. This explains why these complex disorders are often found in clusters in the same families.

Genetic diseases can also be linked to the sex chromosomes, which are the X (female) and Y (male) chromosomes, or mitochondrial DNA. 

List of single gene disorders

There are more than 10,000 known monogenic disorders. As science advances, more single gene disorders could be discovered in the future. Monogenic disorders include3:

• Ehlers-Danlos syndrome (EDS)
• Congenital deafness
• Tay-Sachs disease
• Sickle cell anemia
• Cystic fibrosis
• Familial hypercholesterolemia
• Duchenne muscular dystrophy
• Huntington disease
• Hemochromatosis

What are multifactorial disorders?

Unlike single gene disorders, multifactorial disorders don’t depend exclusively on your DNA. These diseases develop as a result of multifactorial inheritance, which is a combination between genetic predispositions, and other risk factors such as environmental and lifestyle factors.

You can have a higher genetic risk for a multifactorial disease, but your lifestyle and environment will play a significant role in determining whether you actually get the disease or not.

Thanks to modern scientific research, we now know that most common diseases have a genetic component.4 There are many risk factors that impact your chances of getting a multifactorial or multi-gene disorder.

There are certain risk factors that we can change through our own behavior, which are known as modifiable risk factors. These factors include your diet, level of physical activity, weight, smoking, drug or alcohol intake, and sleep hygiene, among others.

On the other hand, there are some factors that can’t be modified, such as your age, biological sex, or ethnicity. But by switching to a healthier lifestyle and taking action against your risk factors, you can significantly lower your likelihood of getting ill.

List of multifactorial disorders

Some of the most common diseases in the world are classified as multifactorial diseases. You can have a higher genetic predisposition to suffer from these diseases, but preventive medicine and a healthy lifestyle can help prevent them. Multifactorial disorders include:

• Hypertension or high blood pressure
• Heart disease
• Heart failure
• Diabetes
• Asthma
• Chronic respiratory diseases
• Obesity
• Allergies
• Osteoporosis
• Alzheimer’s disease
• Epilepsy
• Bipolar disorder
• Schizophrenia
• Skin conditions
• Thyroid disease
• Different types of cancer, such as breast and ovarian
• Neural tube defects
• Hip dysplasia

The role of genes in multifactorial disease

Many of the most common diseases in the world don’t have a single genetic cause, but that doesn’t mean that your genes don’t play a role in their development. As we mentioned above, genetic predisposition can affect your risk of developing multifactorial diseases.

It has been estimated that genetic defects are present in approximately 10% of all adults5, and genetic disease is also a major contributor to pregnancy loss, infant mortality, and even adult hospital admissions. Genetic disorders can have a significant impact on our health and the health of our family. Many people aren’t aware of whether they carry genetic variants, which makes it more difficult to take preventive measures or seek treatment from a younger age.

The reality is that polygenic risk factors + environmental risk factors = multifactorial disease.

But the good news is that learning more about your genome allows you to take action now and prevent future diseases. Even if you have a genetic risk factor for multifactorial disease, there are many things you can start doing today to lower your risk.

Through genomics and preventive medicine, you can develop a strategy that allows you to reduce your health risks. For example, Sequencing.com’s Rare Disease Screen Bundle provides a detailed report on 100% of your DNA information and screens your genes for more than 10,000 diseases.

Sources

1. What are single gene disorders? @Yourgenome · Science Website. Retrieved September 14, 2022. 
2. Finegold, D. N. (2022, August 22). Inheritance of Single-Gene Disorders. MSD Manual Consumer Version. Retrieved September 16, 2022. 
3. Genetic Alliance; District of Columbia Department of Health. Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2010 Feb 17. Appendix G, Single-Gene Disorders. Retrieved September 14, 2022.
4. What are complex or multifactorial disorders? MedlinePlus Genetics. (n.d.-b). Retrieved September 16, 2022.
5. human genetic disease | Definition, Types, & Facts. (2022, July 30). Encyclopedia Britannica. Retrieved September 14, 2022.

About The Author

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of Sequencing.com and the author of Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠ACMG), an Associate of the American College of Preventive Medicine (⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC).