Multifactorial Inheritance

Most common disorders and many interesting human traits are believed to be the cumulative effect of variation among multiple genes, each with a relatively small effect on the phenotype or trait itself.

In contrast to Mendelian traits or chromosomal disorders, "polygenic" or "multifactorial" traits have more complex inheritance patterns. While all genes interact with the environment to a greater or lesser extent to influence the phenotype -- and vice versa -- , the role of environment in multifactorial inheritance is generally considered to be more significant than with Mendelian traits.

Multifactorial, or polygenic, traits...

• are often best visualized as a distribution of a characteristic within a population, such as height or blood pressure;
• have recurrence risks in families that are considerably less than the minimum risk of 25% for a Mendelian autosomal recessive trait; most risk rates have to be determined by empirical studies, but they often fall in the range of 2% to10%, depending on who in a family has been affected and for whom the risk is being calculated.
• are often very complicated to analyze for the number of genes and the environmental factors that are most significantly involved.

A threshold model has often been proposed as a way to explain the inheritance patterns of some multifactorial conditions such as cleft lip with or without cleft palate; schizophrenia; and neural-tube defects. In this model, there is a continuous distribution of a genetically determined liability for a given trait or condition, but only some proportion of individuals above a certain threshold of genetic liability will develop the condition, especially if exposed to environmental factors that can trigger the development of the trait.

Recurrence risks...

• are generally an average and will vary from family to family
• increase with the number of affected relatives
• increase with the severity of the condition
• are higher for children of the less frequently affected sex when there is a difference in the ratio of affected males to affected females in the general population

Recent research has been focusing on determining whether there are specific genes that have greater impact than others within the spectrum of genes at work in a polygenic/multifactorial disorder.