Multifactorial Transmission
Diseases and health traits that involve multiple genes and complex patterns of inheritance are generally described as exhibiting multifactorial transmission. The term multifactorial means many factors. By contrast, simple genetic traits like cystic fibrosis, which are caused by a mutation in a single gene, tend to be inherited in predictable patterns that are either autosomal or sex-linked, and they are either dominant or recessive. Multifactorial traits, however, may involve genes on both autosomes and sex-chromosomes at the same time. Some of the genes may be dominant acting, and others recessive. There may be significant interaction with nongenetic factors like nutrition or other environmental exposures. Traits influenced by multiple genes that do not involve any significant interactions environmental factors are called polygenic traits. When environmental and genetic factors both are involved, the degree of influence attributable to genetics is called heritability. Careful study of identical and fraternal twin pairs is one method of measuring heritability of multifactorial traits.
Multifactorial traits which involve features that can be measured on a continuous numerical scale like weight, blood pressure, or IQ, are called metric traits. Metric traits tend to fit onto a bell-shaped distribution in which there are as many individuals who are above the average as there are below the average. For example, in a population of individuals with an average IQ of 100, there will be approximately the same number of individuals with IQ over 120 as there are individuals with IQ below 80. On average, an individual's measured value will be midway between their values of their biological parents. Naturally, there is considerable variation between different individuals and the actual value may be well above or well below either parent.
Many multifactorial traits do not involve measurable quantifiable variables. An example of this includes structural birth defects such as congenital heart defects. Such traits are called discontinuous or threshold traits. One way to understand these traits is to imagine that there is some measurable variable called liability. How to measure liability is unknown, and like the metric traits, it is distributed on a bell-shaped curve. Everyone has some amount of liability for each of these traits, but a baby will only have the trait or disease if the amount of liability is so high that it exceeds some threshold. Parents of a baby who has the trait typically have higher than average liability, and therefore the chance that their other children will also have the trait is increased.
Considering structural birth defects which have multifactorial transmission, there is some clustering in families, but the numbers of offspring showing the trait are significantly lower than what would be predicted from a single gene model. This is what would be expected from the liability model. Because liability cannot be measured and many different factors may be involved, most cases of these birth defects occur without warning in families without any history of the disorder. Examples of multifactorial traits that cause birth defects include spina bifida, anencephaly, cleft lip, cleft palate, pyloric stenosis, along with many others.
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