Gabriel Bedoya Berrío

Genome-wide association study of Tourette's syndrome

Tourettes syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.

Exploring epistasis in candidate genes for antisocial personality disorder

Objective To identify and characterize high-order gene-to-gene interactions in antisocial personality disorder (ASPD). Methods Participants for case–control study were selected from the inmate male population in Bellavista prison from Medellin. The study included 310 individuals with ASPD and 200 with no ASPD. Diagnoses were made according to a best-estimate procedure based on a semistructured interview (diagnostic interview for genetic studies 3.0). We genotyped some single-nucleotide polymorphisms in candidate genes with main serotonin pathway effects. The gene–gene interaction was examined using the multifactor dimensionality reduction method version 2.0.&agr;. We assessed model sizes of 2 and 3 loci and counted the number of replicates that contained the causal loci in the final best model that was identified using 10-fold cross validation. Results We find epistatic interaction with catechol-O-methyl transferase (COMT), tryptophan hydroxylase, and 5-HTR2A (serotonin receptor) with ASPD. This data supports an important role of polymorphism in serotonin receptors and low enzyme activity of COMT for susceptibility to ASPD. Conclusion This study suggests that gene interactions between genetic variants in COMT, 5-HTR2A and tryptophan hydroxylase gene would be associated with ASPD and influence the dopamine rewards pathways and modulate serotonin levels in ASPD.

Artículo originalPrevalencia de variantes en el gen de la apolipoproteína E (APOE) en adultos de la población general del área urbana de Medellín (Antioquia)Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia)

OBJECTIVE To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. METHODS A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. RESULTS The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. CONCLUSIONS The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.

Asociación de esquizofrenia y sus dimensiones clínicas con el gen NOS1AP en población colombiana

Resumen Introduccion El gen NOS1AP codifica para la proteina adaptadora de oxido nitrico sintasa neuronal 1, que posiblemente esta implicada en la etiopatogenesis de la esquizofrenia. Objetivos Determinar si existe asociacion de variantes en el gen NOS1AP con esquizofrenia y si estas variantes tienen relacion con las dimensiones clinicas del trastorno en poblacion colombiana. Metodologia Es un estudio de casos y controles, con 255 sujetos por grupo. Se tipificaron marcadores dentro del gen NOS1AP y otros informativos de origen genetico, con el fin de ajuster por estratificacion de la poblacion. Se hizo un analisis factorial de componentes principales de cada uno de los items de las escalas de evaluacion de sintomas negativos (SANS) y de sintomas positivos (SAPS) para determinar las dimensiones clinicas. Posteriormente, se evaluo la asociacion de las variantes geneticas con la esquizofrenia y con cada una de las dimensiones. Resultados Se encontro asociacion entre el genotipo C/C del marcador rs945713 con esquizofrenia (OR = 1,79, IC95%: 1,13-2,84). El genotipo C/C de rs945713 se asocio con puntuaciones mas altas en la dimension “aplanamiento afectivo y alogia” y el genotipo A/A del marcador rs4657181 se relaciono con puntuaciones mas bajas en esa misma dimension. Conclusiones Se encontro asociacion significativa de marcadores dentro de NOS1AP con esquizofrenia y la dimension clinica “aplanamiento afectivo y alogia”. Estos resultados son consistentes con estudios previos y apoyan la posibilidad de que NOS1AP influya en la susceptibilidad a esquizofrenia y que sea un modificador de sus caracteristicas clinicas.