I. GENERAL CHARACTERISTICS OF MULTIFACTORIAL DISEASES
Multifactorial diseases are disorders caused by the combined effect of multiple genes (polygenic inheritance) and environmental factors. No single gene mutation is sufficient to cause disease; instead, genetic susceptibility interacts with environmental triggers.
These diseases are the most common causes of morbidity and mortality in human populations.
Key Characteristics
Multifactorial diseases:
- do not follow Mendelian inheritance patterns,
- show familial aggregation, but not clear dominance or recessivity,
- have variable expressivity and incomplete penetrance,
- are influenced by lifestyle, nutrition, infections, toxins, and stress.
Typical examples include:
- hypertension
- diabetes mellitus type 2
- ischemic heart disease
- asthma
Threshold Model of Multifactorial Inheritance
Multifactorial diseases are explained by the liability–threshold model.
Each individual has a certain liability, which is the sum of genetic predisposition and environmental influences. Disease occurs only when this liability exceeds a critical threshold.
Pathogenesis of Multifactorial Diseases
- Multiple susceptibility genes each contribute a small effect.
- Environmental factors add to genetic liability.
- When combined liability exceeds the threshold → disease manifests.
- Severity depends on degree of genetic load and environmental exposure.
- Relatives of affected individuals have higher risk due to shared genes and environment.
Recurrence Risk Features
- Risk is higher in first-degree relatives.
- Risk increases with severity of disease in the proband.
- Risk is higher if the disease affects the less commonly affected sex.