Genetics Northern California

Multifactorial Inheritance

Multifactorial inheritance describes conditions that are caused by a mix of many genetic and environmental factors. These conditions may affect one or more people in a family, but do not follow a typical inheritance pattern. Most often there is no genetic testing recommended for multifactorial conditions. 

Multifactorial = “many factors”
Gene = A sequence of DNA that tells a cell how to work. Genes are passed from parent to child.

Genes play a role in many common conditions, such as cancer, heart disease, and diabetes. There are many different genes that influence these conditions, not just a single gene. These genes also interact with the environment over a person’s lifetime. Factors in the environment that can affect health include diet, exercise levels, exposures, and many other things. Your genetic make-up as well as your environment work together to determine health. 

There are also some birth defects that are multifactorial. Some examples include cleft lip and palate, pyloric stenosis, hip dislocations, heart defects, and spina bifida. These conditions are due to a mix of genetic and environmental factors when a baby is forming during pregnancy.

Recurrence risk
The chance for a multifactorial condition to happen more than once in a family depends on many factors. The risk can be estimated by studying many families with the same condition. This is called an “empiric risk”.  Empiric risks are an average that will vary from family to family.

·       Close relatives are at higher risk.  Family connections may also be called "degrees of relationship”. Your closest relatives (your parents, brothers, sisters, and children) are called first-degree relatives. A person directly connected to a first-degree relative is called a second-degree relative. Second-degree relatives include your grandparents, aunts, uncles, nephews, nieces, and grandchildren. The chance for multifactorial conditions to happen again in the same family is highest for first degree relatives. For example, parents who have one child with a cleft lip have a 3-5% risk for a second child with a cleft. The chance is lower for more distant relatives. A person whose uncle was born with a cleft lip has less than a 1% risk for a cleft in their child.

Degree of relationship

·        The number of relatives with the condition affects the risk.  The risk is higher when there is more than one person in a family with the same condition. For example, if a couple has two children with a multifactorial condition such as a heart defect, any future children of theirs would be at higher risk than a couple who only had one child with a heart defect.  

·        A person’s biologic sex can sometimes affect the risk. For example, pyloric stenosis is a multifactorial condition that is more common in males. When a female has this condition, it suggests more genetic risk in the family. So, the chance for pyloric stenosis is higher in close relatives of a female with that condition and lower in close relatives of a male.  

·        The risk may be higher when a condition is more severe. Multifactorial conditions can range from very mild to very severe. When a condition is very severe, it suggests more genetic risks. For example, when a baby is born with a cleft lip that affects both sides of the lip (bilateral), future brothers or sisters to that child are at a higher risk than if the cleft was only on one side (unilateral).

There is no way to completely prevent multifactorial conditions. You are not able to change the genes you inherit or avoid all risks in the environment. However, it is possible to lower the risk for some conditions by changing the environment.  Here are some examples:

·        Folic acid lowers the risk for some birth defects. : Taking folic acid (a B vitamin) in early pregnancy lowers the risk for birth defects of a baby’s brain (anencephaly) and spine (spinal bifida). It may also lower the chance for heart defects and facial clefts. Folic acid is part of the environment in the womb and helps the neural tube form.  Women who are planning a pregnancy or could become pregnant are advised to get 400 to 800 micrograms (mcg)  of folic acid every day. Learn more: Folic Acid and Your Health

·        Avoiding tobacco smoke lowers the risk for some cancers. Smoking cigarettes or vaping exposes your body to harmful chemicals that can lead to cancer. By stopping (or never smoking), you reduce the exposure to chemicals that make cancer more likely to develop.  Learn more: Quitting Smoking

·        A healthy diet lowers your risk for heart disease.  Eating a diet that includes fruits and vegetables, whole grains, low-fat dairy products, and limits saturated fats and red meats has been shown to benefit your heart health. Learn more: Healthy Eating   

Last Reviewed: November 2020
Reviewed by: Kimberly Barr, MS, LCGC