Many behavioral disorders are likely to be "complex," influenced by several genetic and environmental factors. Although a single gene's variants might thus account for only a portion of the vulnerability to the disorder, the high population frequencies of many of these problems makes understanding such gene variants important for public health. Insights into identifying single gene influences in human complex behavioral disorders have come from family, twin, and adoption studies, mathematical models for complex genetics, identification of candidate genes, elucidation of functional variants in some of the perhaps 40,000 genes expressed in the human brain, and studies in transgenic mice with experimental manipulations of single genes. Modeling studies now suggest that the magnitude of gene effects on a disease is a primary determinant of our ability to identify a disease-associated gene variant. Heritability reflects the proportion of the total interindividual variation due to a gene variant, reflecting both the gene variant's frequency in the population and the size of the effects that the gene variant causes. Sibling relative risk assesses the increased disease risk to siblings that share one-half of the genes with affected probands. Values for heritability, sibling relative risk, environmental contributions, and the power of genetic approaches can be estimated from studies of disease frequencies and patterns in monozygotic and dizygotic twins and in biologically related and adoptive family members.
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