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Multifactorial (Complex) Inheritance

By

David N. Finegold

, MD, University of Pittsburgh

Last full review/revision Jul 2021| Content last modified Jul 2021
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For many traits, expression involves multiple genes. Many such traits (eg, height) distribute as a bell-shaped curve (normal distribution). Normally, each gene adds to or subtracts from the trait independently of other genes. In this distribution, fewer people are at the extremes and many more are in the middle because people are unlikely to inherit multiple factors acting in the same direction. Environmental factors also add to or subtract from the final result.

Many relatively common congenital anomalies and familial disorders result from multifactorial inheritance. In an affected person, the disorder represents the sum of genetic and environmental influences. Risk of the occurrence of such a trait is much higher in 1st-degree relatives (siblings, parents, or children who share, on average, 50% of the affected person’s genes) than in more distant relatives, who are likely to have inherited only a few high-liability genes.

Common disorders with multifactorial inheritance include hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Hypertension , coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more Overview of Coronary Artery Disease , type II diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , cancer, cleft palate Cleft Lip and Cleft Palate Cleft lip, cleft lip and palate, and isolated cleft palate, are collectively termed oral clefts (OCs). OCs are the most common congenital anomalies of the head and the neck with a total prevalence... read more Cleft Lip and Cleft Palate , and arthritis. Many specific genes contributing to these traits are being identified by using the most sensitive genetic tests available (next-generation sequencing Genetic Diagnostic Technologies Genetic diagnostic technology is rapidly improving. A small amount of DNA can be amplified using the polymerase chain reaction (PCR) process, which can produce millions of copies of a gene or... read more ) to test people with and without the traits for mutations. Genetically determined predisposing factors, including a family history and specific biochemical pathways often identified by molecular markers (eg, high cholesterol), can sometimes identify people who are at risk and are likely to benefit from preventive measures.

Multigenic, multifactorial traits seldom produce clear patterns of inheritance; however, these traits tend to occur more often among certain ethnic and geographic groups or among one sex or the other.

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