The discovery of susceptibilil mental disorders

Desearch on the genetic basis of mental monozygotic twins (45%) disorders crossed a major watershed twins (15%). However, 40' this summer. For the first time, specific gotic co-twins of a person genes have been discovered that influence nia are clinically normal ( susceptibility to schizophrenia, a psychosis the risk of illness decreas4 that affects nearly 1% of people throughout genetic relationship more the world and accounts for about 2.5% of be explained by a single g< health-care costs (1). In this issue of PNAS, effects of several such I Chumakov and colleagues (2) describe a inheritance pattern of sc new human gene, G72, on chromosome gested that multiple gen 13q34 that interacts with the gene for Deffect, interacted nonline, amino acid oxidase (DAAO) on 12q24 to other and with environn regulate glutaminergic signaling through influence susceptibility (6 the N-methyl-D-aspartate (NMDA) reception has now been confirn tor pathway. Using traditional positional 20 genomewide linkage sc cloning techniques of linkage and linkage 1,200 families of schizophr disequilibrium, they show that both of these ies found evidence for seve genes are associated with increased suscepeffect; that is, genes that n tibility to schizophrenia. Therefore, this is ity but are neither necessar the first discovery of a specific gene that also cause the disorder. Howe provides a pathogenic molecular mechawas found for any genes nism that can account for the major sympvidual effect, such as a M toms of a psychiatric disorder. Similarly, two of schizophrenia. By 1997 other groups reported this summer that the cations in some, but not a gene dysbindin on 6p22.3 (3) and the gene for susceptibility genes in neuregulin 1 on 8p (4) also influence susmosomes 6p, 8p, and 22q ceptibility to schizophrenia and may operate 5 years of work by man, via the same NMDA mechanism. Each of panded the list of reg these gene discoveries came from associato include target regior tion analysis targeting chromosomal regions 6q21-q22.3, and 13q34, a, first identified by linkage analysis. The sucsistent evidence for broad cess of groups working on three different S5q, 10p, and llq (8). T chromosomal regions of interest confirms locations of the four re( the effectiveness of traditional positional susceptibility genes for s cloning techniques in complex mental disillustrated schematically ii orders. Consequently, these results justify age of schizophrenia to ti optimism for future progress in unraveling the a-7 nicotinic recept( complex disorders in which there is interacreplicated, but does not tion among multiple genetic and environgenic mechanism prodi mental variables. However, it is important symptoms of schizophren to recognize both the strengths and the Until this summer, there limitations of the genetic and functional the positional cloning o strategies used by Chumakov and colleagues gene that could explain the (2). It is also important to recognize the of schizophrenia or any c continuing significance of the prior work ing psychiatric disorder. that laid the foundation for these particular contributions to susceptib experiments. genetic and environmeni Twin and adoption studies demonstrated schizophrenia, linkage ai that susceptibility to schizophrenia is less sensitivity for detectio strongly heritable even if children are reared than does association ar apart from their biological parents. When most efficient design f one twin has schizophrenia, the risk of specific genes in a con schizophrenia in the co-twin is greater in the comparison of cases