For many traits, phenotypic expression involves multiple genes. Many such traits (eg, height) distribute as a bell-shaped curve (normal distribution). Normally, each gene adds to, subtracts from, or otherwise influences the trait independent of other genes. In this distribution, fewer people are at the extremes and the majority are in the middle because people are unlikely to inherit multiple factors acting in the same direction. Environmental factors also influence the final result.
Many relatively common congenital anomalies and familial disorders result from multifactorial inheritance. In an affected person, the disorder represents the totality of genetic and environmental influences. The risk of occurrence of such a trait is much higher in first-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, coronary artery disease, type 2 diabetes mellitus, cancer, 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, genome-wide association studies) 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.
(See also Overview of Genetics.)