Calculating Within-Pair Difference Scores in the Co-twin Control Design. Effects of Alternative Strategies.

Co-twin studies are an elegant and powerful design that allows controlling for the effect of confounding variables, including genetic and a range of environmental factors. There are several approaches to carry out this design. One of the methods commonly used, when contrasting continuous variables, is to calculate difference scores between members of a twin pair on two associated variables, in order to analyse the covariation of such differences. However, information regarding whether and how the different ways of estimating within-pair difference scores may impact the results is scant. This study aimed to compare the results obtained by different methods of data transformation when performing a co-twin study and test how the magnitude of the association changes using each of those approaches. Data was simulated using a direction of causation model and by fixing the effect size of causal path to low, medium, and high values. Within-pair difference scores were calculated as relative scores for diverse within-pair ordering conditions or absolute scores. Pearson's correlations using relative difference scores vary across the established scenarios (how twins were ordered within pairs) and these discrepancies become larger as the within-twin correlation increases. Absolute difference scores tended to produce the lowest correlation in every condition. Our results show that both using absolute difference scores or ordering twins within pairs, may produce an artificial decrease in the magnitude of the studied association, obscuring the ability to detect patterns compatible with causation, which could lead to discrepancies across studies and erroneous conclusions.

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.

BACKGROUND: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. METHODS: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. FINDINGS: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). INTERPRETATION: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. FUNDING: Funding acknowledgements for each cohort can be found in the Supplementary Note.

Genetics of environmental sensitivity to psychiatric and neurodevelopmental phenotypes: evidence from GWAS of monozygotic twins.

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.

A psychophysiological approach to fear appeals. Autonomic, subjective and behavioral responses to health promotion messages / Un enfoque psicofisiológico de los mensajes de miedo. Respuestas autónomas, subjetivas y conductuales a los mensajes de promoción de la salud

A study was designed in order to analyze the effects of fear appeals on psychophysiological, subjective and behavioral responses on the target audience. Three messages on breast cancer, promoting regular mammography screening, elaborated in a similar way to those used by health promotion programs, were presented to ninety-eight women aged 49-50. Messages were of equal length, format and structure but varied in specific clues which distinguished their character (Threat, Surprise, and Standard/control). Psychophysiological reactions (heart rate and frequency of non- specific skin conductance responses) were recorded continuously during message exposure. Self-report measures and personality traits (STAI and EPQ-A) were obtained after viewing the stimulus. There were significant responses to the messages for all psychophysiological measures. The pattern of psychophysiological response, independent of the eliciting message, was significantly related to cancer preventive/detection behavior.(AU)

Se diseñó un estudio para analizar los efectos que tienen las apelaciones al miedo sobre las respuestas psicofisiológicas, subjetivas y conductuales en la población diana. Para ello, se presentaron, a 98 mujeres de 49-50 años de edad, tres mensajes sobre el cáncer de mama promoviendo la realización de mamografía regularmente. Los mensajes fueron elaborados de manera similar a los utilizados por los programas de promoción de la salud. Los tres tenían la misma longitud, formato y estructura, pero variaban en determinadas claves que diferenciaban su carácter (Amenaza, Sorpresa y Estándar/control). Durante la exposición a estos mensajes, se registraron, de manera continua, las respuestas psicofisiológicas (frecuencia cardíaca y frecuencia de respuestas electrodérmicas inespecíficas). Después de ver los estímulos, se tomaron medidas de autoinforme y de personalidad (STAI y EPQ-A). Se encontraron respuestas significativas a los mensajes para todas las medidas psicofisiológicas. Independientemente del mensaje presentado, el patrón de respuesta psicofisiológica se relacionó significativamente con la conducta preventiva de detección del cáncer.(AU)

El Registro de Gemelos de Murcia. Un recurso para la investigación sobre conductas relacionadas con la salud / The Murcia Twin Registry. A resource for research on health-related behaviour

Los diseños genéticamente informativos, y en particular los estudios de gemelos, constituyen la metodología más utilizada para analizar la contribución relativa de los factores genéticos y ambientales a la variabilidad interindividual. Básicamente, consisten en comparar el grado de similitud, con respecto a una característica o rasgo determinado, entre gemelos monocigóticos y dicigóticos. Además de la clásica estimación de heredabilidad, este tipo de registros permite una amplia variedad de análisis únicos por las características de la muestra. El Registro de Gemelos de Murcia es un registro de base poblacional centrado en el análisis de conductas relacionadas con la salud. Las prevalencias de problemas de salud observadas son comparables a las de otras muestras de referencia de ámbito regional y estatal, lo que avala su representatividad. En conjunto, sus características facilitan el desarrollo de diversas modalidades de investigación, además de diseños genéticamente informativos y la colaboración con distintas iniciativas y consorcios (AU)

Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia (AU)

Age and gender effects on the prevalence of poor sleep quality in the adult population / Efecto de la edad y el sexo sobre la prevalencia de una pobre calidad del sueño en población adulta

Objective: Sleep quality has a significant impact on health and quality of life and is affected, among other factors, by age and sex. However, the prevalence of problems in this area in the general population is not well known. Therefore, our objective was to study the prevalence and main characteristics of sleep quality in an adult population sample. Methods: 2,144 subjects aged between 43 and 71 years belonging to the Murcia (Spain) Twin Registry. Sleep quality was measured by self-report through the Pittsburgh Sleep Quality Index (PSQI). Logistic regression models were used to analyse the results. Results: The prevalence of poor sleep quality stands at 38.2%. Univariate logistic regression analyses showed that women were almost twice as likely as men (OR: 1.88; 95% confidence interval [95%CI]: 1.54 to 2.28) to have poor quality of sleep. Age was directly and significantly associated with a low quality of sleep (OR: 1.05; 95%CI: 1.03 to 1.06). Conclusions: The prevalence of poor sleep quality is high among adults, especially women. There is a direct relationship between age and deterioration in the quality of sleep. This relationship also appears to be more consistent in women (AU)

Objetivo: La calidad del sueño tiene una incidencia notable en la salud y en la calidad de vida, y a su vez se ve afectada, entre otros factores, por la edad y el sexo. Sin embargo, la prevalencia de problemas en este ámbito en la población general no es bien conocida. Por ello, nuestro objetivo fue estudiar la prevalencia y las características de la calidad del sueño en una muestra de población adulta. Métodos: 2144 personas de edades comprendidas entre 43 y 71 años pertenecientes al Registro de Gemelos de Murcia. La calidad del sueño se determinó por autoinforme mediante el índice de calidad del sueño de Pittsburgh. Se utilizaron modelos de regresión logística para el análisis de los resultados. Resultados: La prevalencia de una pobre calidad del sueño se sitúa en el 38,2%. Los análisis de regresión logística univariados mostraron que las mujeres prácticamente doblaban (odds ratio [OR]: 1,88; intervalo de confianza del 95% [IC95%]: 1,54-2,28) la probabilidad de tener una pobre calidad del sueño con respecto a los hombres. La edad se asocia de manera directa y significativa con una baja calidad del sueño (OR: 1,05; IC95%: 1,03-1,06). Conclusiones: La prevalencia de una pobre calidad del sueño es alta en la población adulta, en especial en las mujeres. Existe una relación directa entre la edad y el deterioro de la calidad del sueño. Esta relación también parece ser más consistente en las mujeres (AU)

Factores ambientales y genéticos asociados al consumo de psicofármacos en mujeres adultas. Un estudio de gemelos de base poblacional / Environmental and genetic factors associated with psychoactive medication use in adult females. A population-based twin study

Introducción: Nuestro objetivo es determinar la prevalencia de consumo de psicofármacos, en una muestra de mujeres adultas, relacionándolo con variables sociodemográficas y con la presencia de trastornos mentales. Adicionalmente se pretende analizar la contribución relativa de factores ambientales y genéticos a dicho consumo. Método: La muestra consiste en una cohorte, de base poblacional, formada por 437 parejas de gemelas nacidas entre 1940 y 1966. La información se recoge a través de entrevista individual que incluye situación laboral, nivel de estudios, situación de pareja, menopausia, presencia de trastorno mental y consumo de psicofármacos. Se utilizan modelos de regresión logística y se aplica el diseño clásico de estudios de gemelos para estimar la contribución relativa de factores genéticos y ambientales a la variación interindividual. Resultados: En el último mes, el 34,0% de las mujeres entrevistadas habían consumido algún tipo de psicofármaco. El consumo aumenta con la edad, en mujeres inactivas laboralmente, menopáusicas, y que refieren haber padecido trastorno mental. Al controlar por edad, el efecto de todas las variables, a excepción de la presencia de patología, perdía significación. La heredabilidad estimada del consumo de psicofármacos es de un 52%. Esta estimación es similar (46%) para el consumo de las dos categorías estudiadas. Conclusiones: El consumo de psicofármacos en la muestra analizada es elevado. Este consumo se asocia, principalmente a la presencia de trastornos mentales y a la edad. Aproximadamente la mitad de la variación interindividual en el consumo de psicofármacos es atribuible a factores genéticos, mientras que el resto se debería a factores ambientales exclusivos de cada individuo (AU)

Introduction: Our objective is to determine the prevalence and factors associated to psychotropic medication consumption in a sample of adult females. Additionally, this study seeks to analyze the relative contribution of environmental and genetic factors to psychoactive medication use. Method: Sample consists of a population-based cohort comprising 437 pairs of female twins born between 1940 and 1966. Information is collected through individual interviews, and it includes employment status, educational level, partner status, menopause, presence of mental disorders and psychoactive medication use. Logistic regression models are applied. The relative contribution of genetic and environmental factors to interindividual variation is analyzed through the classical twin design. Results: In the past month, 34.0% of the women interviewed had consumed psychoactive medication. Consumption increases with age, in women out of the labor market, menopausal, and reporting a history of mental disorders. When controlling for age, all variables lost significance, except the presence of mental health problems. Heritability estimates for psychoactive medication use was 52%. This estimate is similar (46%) for consumption in the two categories studied. Conclusions: There is a high prevalence of psychoactive medication use in this sample. This consumption is mainly associated with age and presence of mental disorders. About half of the interindividual variation in psychotropic medication use is attributable to genetic factors, while the rest of the variance would be due to environmental factors unique to each individual (AU)

Prevalencia de VIH entre las personas de ocho ciudades españolas que se realizan la serología tras exposiciones heterosexuales, 1992-2003 / HIV prevalence among individuals having had serology performed in eight spanish cities following heterosexual exposure, 1992-2003

Fundamento: La epidemia de infecciones por el virus de la inmunodeficiencia humana (VIH) en España se caracterizó durante los primeros años por el predominio de casos en personas usuarias de drogas inyectadas, pero en la actualidad todo parece apuntar a un progresivo predominio de la transmisión sexual. El objetivo de este trabajo es describir la evolución en la prevalencia de VIH en varios grupos de población heterosexual y caracterizar las situaciones en las que se produjeron las infecciones. Métodos: Estudio descriptivo de las personas que se realizaron la prueba por primera vez en nueve centros de diagnóstico de VIH entre 1992 y 2003 por exposiciones heterosexuales de riesgo, excluyéndose a los usuarios de drogas inyectadas. Resultados: El número de personas en las que se determinó la serología fue de 47.870. La prevalencia de VIH en la población estudiada descendió del 3,2% al 1,0% (p<0,001). En las personas con pareja con diagnóstico de infección por VIH la prevalencia se mantuvo en torno al 10%, en hombres usuarios de prostitución descendió del 1,9% al 1,0% (p=0,049), en las mujeres que ejercen la prostitución del 1,4% al 0,7% (p=0,008), y en el resto de heterosexuales disminuyó del 1,6% al 1,0% en hombres (p=0,014) y del 1,1% al 0,7% en mujeres (p=0,012). Conclusiones: Los resultados indican avances en el control de la transmisión heterosexual del VIH, principalmente en mujeres, aunque todavía se requiere insistir en la prevención (AU)

Background: The human immunodeficiency virus (HIV) epidemic in Spain was characterized throughout the first few years by the predominance of infections among injected drug users (IDU's), but everything currently points to a progressive predominance of sexual transmission. This study is aimed at describing the trend in HIV infection among several heterosexual populations groups and at characterizing the situations in which the infections occurred. Methods: Descriptive study of the individuals who had the test conducted for the first time at nine HIV diagnosis centres within the 1992-2003 period due to high-risk heterosexual exposures, not including injected drug users. Results: A total of 47,870 individuals had serology performed during the period under study. The HIV prevalence among the population under study dropped from 3.2% to 1.0% (p< 0.001). Among the individuals with an HIV infected partners, the prevalence remained at around 10%, the male users of prostitution having dropped from 1.9% to 1.0% (p=0.049); among women involved in prostitution, from 1.4% to 0.7% (p=0.008); and among all other heterosexuals, having dropped from 1.6% to 1.0% among males (p=0.014) and from 1.1% to 0.7% among women (p=0.012). Conclusions: The results indicate advances in the control of heterosexual human immunodeficiency virus transmission, mainly among women, although it is necessary to still continue stressing prevention (AU)