ABSTRACT
The importance of genetics in understanding the etiology of mental illness has become increasingly clear in recent years, as more evidence has mounted that almost all neuropsychiatric disorders have a genetic component. It has also become clear, however, that these disorders are etiologically complex, and multiple genetic and environmental factors contribute to their makeup. So far, traditional linkage mapping studies have not definitively identified specific disease genes for neuropsychiatric disorders, although some potential candidates have been identified via these methods (e.g. the dysbindin gene in schizophrenia; Straub et al., 2002; Schwab et al., 2003). For this reason, alternative approaches are being attempted, including studies in genetically isolated populations. Because isolated populations have a high degree of genetic homogeneity, their use may simplify the process of identifying disease genes in disorders where multiple genes may play a role. Several areas of Latin America contain genetically isolated populations that are well suited for the study of neuropsychiatric disorders. Genetic studies of several major psychiatric illnesses, including bipolar disorder, major depression, schizophrenia, Tourette Syndrome, alcohol dependence, attention deficit hyperactivity disorder, and obsessive-compulsive disorder, are currently underway in these regions. In this paper we highlight the studies currently being conducted by our groups in the Central Valley of Costa Rica to illustrate the potential advantages of this population for genetic studies.
Subject(s)
Genetic Drift , Mental Disorders/epidemiology , Models, Genetic , Social Isolation , Attitude to Health , Bipolar Disorder/epidemiology , Bipolar Disorder/genetics , Chromosomes, Human/genetics , Costa Rica/epidemiology , Humans , Indians, Central American/genetics , Mental Disorders/genetics , Prejudice , Schizophrenia/epidemiology , Schizophrenia/genetics , Spain/ethnology , Tourette Syndrome/epidemiology , Tourette Syndrome/geneticsSubject(s)
Adaptor Proteins, Signal Transducing , Carrier Proteins/genetics , Deafness/genetics , Adolescent , Adult , Age of Onset , Child , Deafness/diagnosis , Disease Progression , Female , Formins , Humans , Male , Pedigree , PhenotypeABSTRACT
Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype.
