The sub‐discipline of genetic epidemiology focuses on identification of the role of genetic factors and their joint influence with environmental factors in disease etiology. Genetic epidemiology employs traditional epidemiologic study designs including case‐control and cohort studies to evaluate the aggregation of disorders in groups as closely related as twins or as loosely related as migrant cohorts. Prior to the molecular genetic era, study designs in genetic epidemiology were designed to infer genetic causation by controlling for genetic background while letting the environment vary (eg, half‐siblings, separated twins) or conversely, controlling for the environment while allowing variance in the genetic background (eg, siblings, twins, adoptees, nonbiologic siblings). 63 Investigations in genetic epidemiology are typically based on a combination of study designs including family, twin and adoption studies. As described below, sophisticated methods have recently been developed to compare combinations of genetic markers between cases and controls (eg, polygenic risk scores, PRS), and to conduct genome‐wide complex trait analysis (GCTA), that estimates the proportion of phenotypic variance explained by genetic variants (typically single nucleotide polymorphisms, SNPs) for complex traits. 64 Some additional genetic epidemiology terminology is included in Box 1.
