Vitamin D receptor gene polymorphisms have negligible effect on human height.

Human 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 (Bsml) 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 [Fokl] 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 similar to 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

Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented

Methods of synthesizing qualitative research studies for health technology assessment

OBJECTIVES Synthesizing qualitative research is an important means of ensuring the needs, preferences, and experiences of patients are taken into account by service providers and policy makers, but the range of methods available can appear confusing. This study presents the methods for synthesizing qualitative research most used in health research to-date and, specifically those with a potential role in health technology assessment. METHODS To identify reviews conducted using the eight main methods for synthesizing qualitative studies, nine electronic databases were searched using key terms including meta-ethnography and synthesis. A summary table groups the identified reviews by their use of the eight methods, highlighting the methods used most generally and specifically in relation to health technology assessment topics. RESULTS Although there is debate about how best to identify and quality appraise qualitative research for synthesis, 107 reviews were identified using one of the eight main methods. Four methods (meta-ethnography, meta-study, meta-summary, and thematic synthesis) have been most widely used and have a role within health technology assessment. Meta-ethnography is the leading method for synthesizing qualitative health research. Thematic synthesis is also useful for integrating qualitative and quantitative findings. Four other methods (critical interpretive synthesis, grounded theory synthesis, meta-interpretation, and cross-case analysis) have been under-used in health research and their potential in health technology assessments is currently under-developed. CONCLUSIONS Synthesizing individual qualitative studies has becoming increasingly common in recent years. Although this is still an emerging research discipline such an approach is one means of promoting the patient-centeredness of health technology assessments

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes

Similarities in drinking behavior of twin's friends: moderation of heritability of alcohol use

Previous research has indicated that friends' drinking may influence alcohol use in adolescents and young adults. We explored whether similarities in the drinking behavior of friends of twins influence the genetic architecture of alcohol use in adolescence and young adulthood. Survey data from The Netherlands Twin Register were available for 1,526 twin pairs aged 16-25 years. We categorized the twin pairs as concordant (both report similar alcohol use in their friends) or discordant for the alcohol use of their friends. Genetic moderator models were tested by carrying out multi-group analyzes in Mplus. Findings showed a significant moderation effect. Genetic factors were more and common environment less important in the explanation of variation in alcohol use in twins discordant for alcohol use of friends than in twins concordant for alcohol use of friend

The Dopaminergic Reward System and Leisure Time Exercise Behavior: A Candidate Allele Study

Purpose. Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680) and three variable number of tandem repeats (VNTRs in DRD4, upstream of DRD5, and in DAT1) were investigated for an association with regular leisure time exercise behavior. Materials and Methods. Data on exercise activities and at least one SNP/VNTR were available for 8,768 individuals aged 7 to 50 years old that were part of the Netherlands Twin Register. Exercise behavior was quantified as weekly metabolic equivalents of task (MET) spent on exercise activities. Mixed models were fitted in SPSS with genetic relatedness as a random effect. Results. None of the genetic variants were associated with exercise behavior (P > .02), despite sufficient power to detect small effects. Discussion and Conclusions. We did not confirm that allelic variants involved in dopaminergic function play a role in creating individual differences in exercise behavior. A plea is made for large genome-wide association studies to unravel the genetic pathways that affect this health-enhancing behavior

Thought Problems from Adolescence to Adulthood: Measurement Invariance and Longitudinal Heritability

This study investigates the longitudinal heritability in Thought Problems (TP) as measured with ten items from the Adult Self Report (ASR). There were ~9,000 twins, ~2,000 siblings and ~3,000 additional family members who participated in the study and who are registered at the Netherlands Twin Register. First an exploratory factor analysis was conducted to examine the underlying factor structure of the TP-scale. Then the TP-scale was tested for measurement invariance (MI) across age and sex. Next, genetic and environmental influences were modeled on the longitudinal development of TP across three age groups (12–18, 19–27 and 28–59 year olds) based on the twin and sibling relationships in the data. An exploratory factor analysis yielded a one-factor solution, and MI analyses indicated that the same TP-construct is assessed across age and sex. Two additive genetic components influenced TP across age: the first influencing TP throughout all age groups, while the second arises during young adulthood and stays significant throughout adulthood. The additive genetic components explained 37% of the variation across all age groups. The remaining variance (63%) was explained by unique environmental influences. The longitudinal phenotypic correlation between these age groups was entirely explained by the additive genetic components. We conclude that the TP-scale measures a single underlying construct across sex and different ages. These symptoms are significantly influenced by additive genetic factors from adolescence to late adulthood

Common Variants in the Type 2 Diabetes KCNQ1 Gene Are Associated with Impairments in Insulin Secretion During Hyperglycaemic Glucose Clamp

Background: Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients. Methodology: The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp. Principal Findings: We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07-1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications. Conclusions: Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism