Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Background and aims: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. Methods: A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. Results: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. Conclusion: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

Tools of genomic medicine for clinical practice: The example of psychiatry. / Herramientas de la medicina genómica para la práctica clínica: el ejemplo de la psiquiatría.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

La mayoría de los trastornos psiquiátricos tienen una heredabilidad de moderada a alta, con diferentes arquitecturas genéticas. Aunque la investigación genética en psiquiatría ha tenido un avance progresivo, sus hallazgos, interpretación e impacto en la psiquiatría clínica resultan desconocidos para la mayoría de los profesionales de salud mental. En este artículo se abordan conceptos clave sobre genética para el entendimiento de algunas entidades clínicas, con énfasis en la nomenclatura genética y los tipos de mutaciones. Particularmente, se plantea el rol de la herencia en los inicios de la investigación genética en psiquiatría, los diseños de estudio más utilizados y sus principales objetivos. Por otro lado, se revisan algunas bases de datos genéticas y genómicas que pueden ser de utilidad para la práctica clínica. Entre ellas destacan , ClinVar, Ensembl y . Finalmente, se plantea una viñeta clínica en donde es posible aplicar algunas de las herramientas de la medicina genómica. Debido a que la evidencia en genética psiquiátrica se basa en estudios realizados en poblaciones con origen ancestral europeo o norteamericano, es de suma relevancia desarrollar estudios locales para incrementar el conocimiento y la aplicación de la medicina genómica sobre poblaciones subrepresentadas.

Herramientas de la medicina genómica para la práctica clínica: el ejemplo de la psiquiatría / Tools of genomic medicine for clinical practice: The example of psychiatry

La mayoría de los trastornos psiquiátricos tienen una heredabilidad de moderada a alta, con diferentes arquitecturas genéticas. Aunque la investigación genética en psiquiatría ha tenido un avance progresivo, sus hallazgos, interpretación e impacto en la psiquiatría clínica resultan desconocidos para la mayoría de los profesionales de salud mental. En este artículo se abordan conceptos clave sobre genética para el entendimiento de algunas entidades clínicas, con énfasis en la nomenclatura genética y los tipos de mutaciones. Particularmente, se plantea el rol de la herencia en los inicios de la investigación genética en psiquiatría, los diseños de estudio más utilizados y sus principales objetivos. Por otro lado, se revisan algunas bases de datos genéticas y genómicas que pueden ser de utilidad para la práctica clínica. Entre ellas destacan , ClinVar, Ensembl y . Finalmente, se plantea una viñeta clínica en donde es posible aplicar algunas de las herramientas de la medicina genómica. Debido a que la evidencia en genética psiquiátrica se basa en estudios realizados en poblaciones con origen ancestral europeo o norteamericano, es de suma relevancia desarrollar estudios locales para incrementar el conocimiento y la aplicación de la medicina genómica sobre poblaciones subrepresentadas.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

Autosomal Recessive Cerebellar Ataxia 1: First Case Report Depicting a Variant in SYNE1 Gene in a Chilean Patient.

Autosomal recessive cerebellar ataxia type 1 (ARCA-1) or spinocerebellar ataxia autosomal recessive type 8 (SCAR8) is a slowly progressive neurodegenerative disorder that occurs due to mutations in the spectrin repeat containing nuclear envelope protein 1 (SYNE1) gene. Previously considered a rare cause of ARCA, related to French-Canadian patients from Beauce, Quebec, Canada, SYNE1 ataxia is now known to be of worldwide distribution. We present the case report of a 54-year-old male patient with the genetic diagnosis of SYNE1 ataxia, presenting with a SYNE1 gene mutation never described in Chilean population before.

Beyond the Categorical Distinction Between Borderline Personality Disorder and Bipolar II Disorder Through the Identification of Personality Traits Profiles.

BACKGROUND: The relationship between borderline personality disorder (BPD) and type-II bipolar disorder (BDII) is not clearly understood. Nevertheless, in clinical practice and research, most efforts focus on establishing a categorical distinction between the two. We propose using personality traits as a more informative strategy to describe them. METHODS: Five-Factor Model personality traits were measured in 73 individuals with either BPD or BDII. Latent class cluster analysis was applied to the sample. RESULTS: A three-cluster model resulted the best fit to the data, where all clusters had high neuroticism and low extraversion scores but differed widely on the other traits. The clusters' boundaries did not match the categorical diagnosis. CONCLUSIONS: Our sample showed significant heterogeneity on personality traits, which can have a relevant effect on the outcome of each disorder and that was not captured by the categorical diagnosis. Thus, we advocate for a multivariate approach as a better way to understand the relationship between BPD and BDII.

Lack of Association between the IL6R Gene Asp358Ala Variant (rs2228145), IL-6 Plasma Levels, and Treatment Resistance in Chilean Schizophrenic Patients Treated with Clozapine.

Alterations in neuroinflammatory processes have been suggested to contribute to the development of Schizophrenia (SZ); one component of the inflammatory system that has been linked to this disorder is interleukin-6 (IL-6). The minor allele of rs2228145, a functional polymorphism in the IL-6 receptor gene, has been associated to elevated IL-6 plasma levels and increased inflammatory activity, making it an interesting candidate to study as a possible factor underlying clinical heterogeneity in SZ. We studied a sample of 100 patients undergoing treatment with clozapine. Their symptoms were quantified by Brief Psychotic Rating Scale; those with the lowest scores ("remitted") were compared with the highest ("clozapine treatment resistant"). We determined allelic frequencies for rs2228145 and IL-6 plasma levels. Our results do not support a role of IL-6 in response to treatment with clozapine. Further studies accounting for potential confounding factors are necessary.

Commentary to medical genetics and genomic medicine in Chile: Chilean experience on molecular diagnosis for neurodegenerative disorders.

In this article, the experience in the molecular diagnosis in neurodegenerative disorders in Chile, including present challenges and potential new pathways for development, is explained.

Fluoxetine response in impulsive-aggressive behavior and serotonin transporter polymorphism in personality disorder.

BACKGROUND: Disturbances in central serotonin function have been implicated in impulsive and aggressive behavior. A deletion/insertion polymorphism within the 5-HT transporter promoter gene (5-HTTLPR) is thought to be associated with disturbed impulse control, anxiety, and depression. The serotonin transporter (5-HTT) is the primary action site for selective serotonin reuptake inhibitors (SSRIs). Several studies of major depression have shown that the l allele of 5-HTTLPR is associated with better SSRI antidepressant effects than the s allele. METHODS: This study investigates the association between response of impulsivity to treatment with fluoxetine and 5-HTTLPR polymorphism in 49 personality disordered patients. Additionally, we studied TPH1, 5HT1B and 5HT2C receptor polymorphisms as predictors of response in this population. RESULTS: Results reveal that patients with the l/l genotype of 5-HTTLPR had a significantly better response to fluoxetine when compared to s allele carriers, as evaluated on the basis of total (P<0.05) and Aggression subscale (P<0.01) Overt Aggression Scale Modified-score percentage change. There were no significant associations between fluoxetine response and TPH1 (A218C) (-6525 A>G) (-5806 G>T), HTR1B (G861C) and HTR2C (G68C) genotype groups. CONCLUSION: This is the first study assessing the association between these polymorphisms and anti-impulsive response to fluoxetine in personality disorder. As the s genotype is associated with a poorer selective serotonin reuptake inhibitors response in major depression, bulimia nervosa and borderline personality disorder, it could represent a common biological background for SSRI response.

Relaciones entre el trastorno límite de personalidad y el espectro bipolar: [revisión] / Relationship between borderline personality disorder and bipolar spectrum: [review]

Existe una controversia respecto a la independencia nosológica del trastorno límite de personalidad. Algunos autores sostienen que es parte del trastorno bipolar, mientras otros afirman que es una entidad independiente. En este trabajo se analiza la evolución histórica de los conceptos de trastorno límite y trastorno bipolar. Se discuten los argumentos a favor y en contra de incluir el trastorno límite dentro del trastorno bipolar. Por último se proponen nuevas estrategias para abordar este problema.

The independent nosological status of borderline personality disorder is a controversial issue. Some authors consider borderline as part of bipolar spectrum, but other sustain that is a independent entity. The historical evolution of borderline personality disorder and bipolar disorder is analyzed in this work. The arguments for include, or not include, borderline personality disorder in bipolar disorder is discussed. Finally, new strategies for study this problem are proposed.

Estudio farmacogenómico en trastorno límite de personalidad / Borderline personality disorder: a pharmacogenomic study

Antecedentes: Las conductas agresivas e impulsivas han sido asociadas con disfunciones del sistema serotoninérgico central. Polimorfismos del transportador de serotonina, de la triptófano hidroxilasa (TPH1) y de los receptores serotoninérgicos 5HT1B y 5HT2C han sido vinculados a agresión e impulsividad. Varios estudios en depresión mayor han demostrado que el alelo corto (S) del promotor del gen transportador de serotonina se asocia a una peor respuesta a los inhibidores selectivos de la recapacitación de serotonina (ISNS). Material y métodos: En este estudio se investigó la asociación entre la respuesta de la impulsividad al tratamiento con fluoxetina y polimorfismos del transportador de serotonina, TPH1 y de los receptores 5HT1B y 5HT2C, en 49 pacientes con trastorno límite de personalidad. Resultados: Los pacientes con el genotipo L/L del promotor del gen transportador de serotonina, evaluados mediante la Overt Aggression Scale-Modified (OAS-M), tuvieron una respuesta a fluoxetina significativamente mejor que los portadores del alelo S. No se encontró asociación entre la respuesta a fluoxetina y los genotipos de TPH1 y de los receptores 5HT1B y 5HT2C. Conclusiones: Este es el primer estudio en el que se evalúa la asociación entre estos polimorfismos y la respuesta anti-impulsiva a la fluoxetina en pacientes con trastorno límite de personalidad. El alelo S puede representar un factor común de peor respuesta a los ISRS en enfermedades asociadas a una disfunción serotoninérgica.

Background: Disturbances in central serotonin function have been implicated in impulsive and aggressive behavior. Serotonin transporter tryptophan hydroxylase (TPH1) and serotoninergic receptor (5HT1B, 5HT2C) polymorphisms have been linked to aggression and impulsivity. Several studies of major depression have shown that the short allele (S) of the serotonin transporter promoter gene is associated with a worse response to selective serotonin reuptake inhibitors (SSRIs). Material and methods: This study investigates the association between the response of impulsivity to fluoxetine treatment and serotonin transporter, TPH1 and 5HT1B and 5HT2C receptor polymorphisms in 49 patients with borderline personality disorder. Results: Patients with the Long/Long (L/L) genotype of the serotonin transporter promoter had a significantly better response to fluoxetine when compared to the S allele carriers, as evaluated by the Overt Aggression Scale-Modified (OAS-M). There were no significant associations between these polymorphisms and anti-impulsive response to fluoxetine in patients with borderline personality disorder. The S allele may represent a common factor of worse response to SSRIs in diseases associated to serotonin dysfunction.