Multifactorial

Multifactorial refers to traits, conditions, or diseases that arise from the combined influence of multiple genetic and environmental factors. Unlike single-gene (Mendelian) disorders, multifactorial traits are typically continuous or show varying degrees of expression, and no single factor is sufficient to cause the outcome.

Genetic architecture: many genes with small effects (polygenic), interacting with environmental factors such as diet, lifestyle, or exposures. The liability-threshold model is often used: individuals carry an underlying susceptibility (liability) from gene variants and environment; when liability exceeds a threshold, the trait manifests. Heritability estimates measure how much of variation in a population is due to genetic factors, but they do not determine individual risk.

Common examples: height; body mass index; blood pressure; type 2 diabetes; coronary artery disease; neural tube defects; several psychiatric and neurodevelopmental disorders including schizophrenia and autism show multifactorial contributions.

Research methods: genome-wide association studies (GWAS) identify many associated loci with small effects; polygenic risk scores aggregate effects across loci to estimate individual risk; twin and family studies inform heritability and environmental influence; gene-environment interaction analyses examine how genetic risk interacts with exposures.

Clinical and ethical implications: risk assessment often relies on family history and population risk; counseling should emphasize probabilistic, not deterministic, risk; prevention focuses on modifiable environmental factors; the term underscores complexity and variability across populations.