"A gene for...": the nature of gene action in psychiatric disorders.
A central phrase in the new "GeneTalk" is "X is a gene for Y," in which X is a particular gene on the human genome and Y is a complex human disorder or trait. This article begins by sketching the historical origins of this phrase and the concept of the gene-phenotype relationship that underlies it. Five criteria are then proposed to evaluate the appropriateness of the "X is a gene for Y" concept: 1) strength of association, 2) specificity of relationship, 3) noncontingency of effect, 4) causal proximity of X to Y, and 5) the degree to which X is the appropriate level of explanation for Y. Evidence from psychiatric genetics is then reviewed that address each of these criteria. The concept of "a gene for..." is best understood as deriving from preformationist developmental theory in which genes-like preformationist anlagen-"code for" traits in a simple, direct, and powerful way. However, the genetic contribution to psychiatric disorders fails to meet any of the five criteria for the concept of "X is a gene for Y." The impact of individual genes on risk for psychiatric illness is small, often nonspecific, and embedded in complex causal pathways. The phrase "a gene for..." and the preformationist concept of gene action that underlies it are inappropriate for psychiatric disorders.
Kendler
Kenneth S
KS
Department of Psychiatry, Virginia Institute for Psychiatry and Behavioral Genetics, Medical College of Virginia-Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298-0126, USA. kendler@hsc.vcu.edu
D005786:Gene Expression Regulation / Q000235:genetics; D005826:Genetics, Medical / Q000592:standards*; D040941:Heredity; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D010641:Phenotype