Suchergebnisse

AbstractHuman height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1521] polymorphisms). We genotyped large Caucasian samples from Australia (N= 3906) and the Netherlands (N= 1689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3cm) to the effect observed in the published adult meta-analysis. An effect of this size explains ~0.1% of the phenotypic variance in height — this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height.

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.

Over the past 25 years, the Adult Netherlands Twin Register (ANTR) has collected a wealth of information on physical and mental health, lifestyle, and personality in adolescents and adults. This article provides an overview of the sources of information available, the main research findings, and an outlook for the future. Between 1991 and 2012, longitudinal surveys were completed by twins, their parents, siblings, spouses, and offspring. Data are available for 33,957 participants, with most individuals having completed two or more surveys. Smaller projects provided in-depth phenotyping, including measurements of the autonomic nervous system, neurocognitive function, and brain imaging. For 46% of the ANTR participants, DNA samples are available and whole genome scans have been obtained in more than 11,000 individuals. These data have resulted in numerous studies on heritability, gene x environment interactions, and causality, as well as gene finding studies. In the future, these studies will continue with collection of additional phenotypes, such as metabolomic and telomere length data, and detailed genetic information provided by DNA and RNA sequencing. Record linkage to national registers will allow the study of morbidity and mortality, thus providing insight into the development of health, lifestyle, and behavior across the lifespan.