Suchergebnisse

AbstractThe Thought–Problem scale (TP) of the CBCL assesses symptoms such as hallucinations and strange thoughts/behaviors and has been associated with other behavioral disorders. This study uses parental reports to examine the etiology of variation in TP, about which relatively little is known, in 7-year-old twins. Parental ratings on TP were collected in 8,962 7-year-old twin pairs. Because the distribution of TP scores was highly skewed scores were categorized into 3 classes. The data were analyzed under a threshold liability model with genetic structural equation modeling. Ratings from both parents were simultaneously analyzed to determine the rater agreement phenotype (or common phenotype [TPc]) and the rater specific phenotype [TPs] that represents rater disagreement caused by rater bias, measurement error and/or a unique view of the parents on the child's behavior. Scores on the TP-scale varied as a function of rater (fathers rated fewer problems), sex (boys scored higher) and zygosity (DZ twins scored higher). The TPc explained 67% of the total variance in the parental ratings. Variation in TPc was influenced mainly by the children's genotype (76%). Variance in TPs also showed a contribution of genetic factors (maternal reports: 61%, paternal reports: 65%), indicating that TPs does not only represent rater bias. Shared environmental influences were only found in the TPs. No sex differences in genetic architecture were observed. These results indicate an important contribution of genetic factors to thought problems in children as young as 7 years.

AbstractIn 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected. Fertile women were bled on day 2–4 of the menstrual cycle, or in their pill-free week. Biological samples were collected for DNA isolation, gene expression studies, creation of cell lines and for biomarker assessment. At the time of blood sampling, additional phenotypic information concerning health, medication use, body composition and smoking was collected. Of the participants contacted, 69% participated. Blood and urine samples were collected in 9,530 participants (63% female, average age 44.4 (SD 15.5) years) from 3,477 families. Lipid profile, glucose, insulin, HbA1c, haematology, CRP, fibrinogen, liver enzymes and creatinine have been assessed. Longitudinal survey data on health, personality and lifestyle are currently available for 90% of all participants. Genome-wide SNP data are available for 3,524 participants, with additional genotyping ongoing. The NTR biobank, combined with the extensive phenotypic information available within the NTR, provides a valuable resource for the study of genetic determinants of individual differences in mental and physical health. It offers opportunities for DNA-based and gene expression studies as well as for future metabolomic and proteomic projects.

We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.