The
liability-threshold model is a threshold model of categorical (usually binary) outcomes in which a large number of variables are summed to yield an overall 'liability' score; the observed outcome is determined by whether the
latent score is smaller or larger than the threshold. The liability-threshold model is frequently employed in medicine and genetics to model risk factors contributing to disease. In a genetic context, the variables are all the genes and different environmental conditions, which protect against or increase the risk of a disease, and the threshold
z is the biological limit past which disease develops. The threshold can be estimated from population prevalence of the disease (which is usually low). Because the threshold is defined relative to the population & environment, the liability score is generally considered as a N(0, 1)
normally distributed random variable. Early genetics models were developed to deal with very rare genetic diseases by treating them as
Mendelian diseases caused by 1 or 2 genes: the presence or absence of the gene corresponds to the presence or absence of the disease, and the occurrence of the disease will follow predictable patterns within families. Continuous traits like height or intelligence could be modeled as
normal distributions, influenced by a large number of genes, and the
heritability and effects of selection easily analyzed. Some diseases, like alcoholism, epilepsy, or
schizophrenia, cannot be Mendelian diseases because they are common; do not appear in Mendelian ratios; respond slowly to selection against them; often occur in families with no prior history of that disease; however, relatives and adoptees of someone with that disease are far more likely (but not certain) to develop it, indicating a strong genetic component. The liability threshold model was developed to deal with these non-Mendelian binary cases; the model proposes that there is a continuous normally-distributed trait expressing risk polygenically influenced by many genes, which all individuals above a certain value develop the disease and all below it do not. The first threshold models in genetics were introduced by
Sewall Wright, examining the propensity of
guinea pig strains to have an extra hind toe, a phenomenon which could not be explained as a dominant or recessive gene, or continuous "
blending inheritance". The modern liability-threshold model was introduced into human research by geneticist
Douglas Scott Falconer in his textbook and two papers. Falconer had been asked about the topic of modeling 'threshold characters' by
Cyril Clarke who had
diabetes. An early application of liability-threshold models was to schizophrenia by
Irving Gottesman &
James Shields, finding substantial heritability & little shared-environment influence and undermining the "cold mother" theory of schizophrenia. ==Global boiling==