Psychiatric disorders show a complex pattern of inheritance with genetic and environmental factors influencing disease risk. Despite the existence of numerous association studies aiming to identify genetic variants involved in these disorders, inconsistencies in replication studies are common and just a few examples of links between gene variants and psychiatric disorders have been accepted. Several factors may be underlying the failure on replication: difficulties on the definition of clinical phenotypes, existence of distinct disease incidences or disease susceptibility variants among populations and, finally, differences in Linkage Disequilibrium and allele frequencies because of diverse population history. Whole genome association studies (WGAS) are powerful methods to map disease genes, however, these expensive techniques have been unsuccessful for psychiatric disorders. An alternative approach could be the use of mapping by admixture linkage disequilibrium (MALD), an efficient and economical method to localize disease-causing variants between two historically separated populations. MALD has already been successful for identification of disease loci in African American populations and, similarly, it is hoped to be a powerful tool in Latin American populations. We propose the design of an admixture panel of SNPs to map susceptibility genes for psychiatric disorders, particularly substance use and attention-deficit hyperactivity disorders, by the analysis of native (Aymara) and recently admixed populations from Chile. Furthermore, we also plan to assess the repercussions that different genetic structures among populations may have on the interpretation of association studies and, finally, we will search for signals of natural selection and adaptation pinpointing potential genes affecting behavioural traits. This collaborative and interdisciplinary project will also focus on the anthropological and cultural implications of the research and results obtained.
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