Лингвистическая корректность и достоверность содержания русской версии модуля гастроинтестинальных симптомов опросника PedsQL™ для пациентов педиатрического профиля

Background. Health Related Quality of Life (HRQL) is a person’s perception of the effect of a disease on physical, social and psychological functioning and wealth. Questionnaires that help assess the HRQL can give a concept of child’s state, identify arcane issues and they are of great importance for a full understanding of how the state of health affects the child. Universal HRQL tools allow to compare results with general parameters, indicators with specific symptoms better reflect clinically significant moments. The most widespread in the Russian Federation was the general PedsQLTM 4.0 questionnaire, widely used in practice to assess HRQL in children with various pathologies. Objective.The aim of the study is to describe the analysis of linguistic accuracy and authenticity of the content of the Russian version of the module of gastrointestinal symptoms of the PedsQLTM questionnaire, measuring HRQL, in children with gastrointestinal disorders (GIDs).Materials and methods. The establishment of linguistic accuracy and authenticity of the content was carried out according to international standards. The process included forward translation, scientific assessment and coordination, reverse translation, verification of the reverse translation and interviews with 17 children aged 5–18 years with symptoms of GIDs and 20 parents of children with symptoms of GIDs aged 2–18 years.Results. The Russian version of PedsQLTM module of gastrointestinal symptoms (report from children 5-18 years old, report from parents for children 2–18 years old) was developed without significant difficulties. Eight questions required discussion after the forward translation, one change was made after the reverse translation, and three changes were made after the study of the symptom’s module by patients and parents.Conclusion. A conceptually equivalent version of the of PedsQLTM module of gastrointestinal symptoms in Russian has been developed for children aged 2–18 years. It allows to improve the assessment of HRQL in children with GIDs in the Russian Federation. To assess authenticity and reliability of the Russian version of the module, it’s recommended to conduct further research using a larger sampleОбоснование. Качество жизни, связанное со здоровьем (КЖСЗ) — это восприятие человеком влияния болезни на физическое, социальное и психологическое функционирование и благосостояние. Опросники, которые помогают оценивать КЖСЗ, могут дать представление о состоянии ребенка, выявить скрытые проблемы и имеют большое значение для полного понимания того, как влияет состояние здоровья на ребенка. Универсальные инструменты исследования КЖСЗ позволяют сравнивать результаты с общими параметрами, показатели со специфичными симптомами лучше отражают клинически значимые моменты. Наибольшую распространенность в Российской Федерации получил общий опросник PedsQL™ 4.0, широко используемый в практике для оценки КЖСЗ у детей с различной патологией.Цель исследования— описать анализ лингвистической корректности и достоверности содержания русской версии модуля гастроинтестинальных симптомов опросника PedsQL™, измеряющих КЖСЗ, у детей с расстройствами желудочно-кишечного тракта (ЖКТ).Материалы и методы. Установление лингвистической корректности и соответствия содержанию проводилось по международным стандартам. Процесс включал в себя прямой перевод, экспертную оценку и согласование, обратный перевод, проверку обратного перевода и интервью с 17 детьми в возрасте 5–18 лет с симптомами заболеваний ЖКТ и 20 родителями детей с симптомами заболеваний ЖКТ в возрасте 2–18 лет.Результаты. Русская версия модуля гастроинтестинальных симптомов PedsQL™ (отчет детей 5–18 лет, отчет родителей для детей 2–18 лет) была разработана без значимых трудностей. Восемь вопросов потребовали обсуждения после прямого перевода, после обратного перевода было внесено одно изменение, а после изучения модуля симптомов пациентами и родителями — три изменения.Заключение. Была разработана концептуально эквивалентная версия модуля симптомов PedsQL™ на русском языке для детей в возрасте 2–18 лет. Она позволяет улучшить оценку КЖСЗ у детей с расстройствами ЖКТ в Российской Федерации. Для оценки достоверности и надежности русскоязычной версии модуля рекомендуется проведение дальнейших исследований с использованием большей выборки

A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (∼90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10 −8 ; OR 0.82) that was validated when combined with genotype data from a replication cohort ( P = 8.62 × 10 −9 ; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10 −9 ; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ∼12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

<p>Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.</p>

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.c.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders

Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

The final version of this article is available from Nature Publishing Group at https://doi.org/10.1038/nn.3922.Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders