Further evidence for a QTL influencing body mass index on chromosome 7p from a genome-wide scan in Dutch families.

Obesity is a rapidly growing threat to public health, driven by the increased occurrence of high caloric diets and sedentary lifestyles. Within this environment, genetic influences may largely determine inter-individual differences in obesity-related traits. To map genes involved in weight regulation, we performed a genome-wide linkage scan for body mass index (BMI), a reliable measure of total body fat, in 192 Dutch families including 315 twins and 210 siblings with data on BMI. Using variance components linkage analysis, regions with LOD-scores greater than 2 were observed on 6p25.1 (LOD-score, 2.13) and 7p21.1 (LOD-score, 2.40). LOD-scores higher than 1 were found on chromosomes 3, 13, 15 and 21. Of note, evidence for the putative quantitative trait locus for BMI on 7p was obtained previously from such diverse populations as Mexican-Americans, Asians and Nigerians, suggesting that the underlying genes may effect weight regulation in diverse environments. An obvious positional candidate in the 7p linkage region is the gene encoding neuropeptide Y (NPY) that controls satiety and food intake

High microsatellite and SNP genotyping success rate established in a large number of genomic DNA samples extracted from mouth swabs and genotypes

In this article, we present the genomic DNA yield and the microsatellite and single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA extracted from a large number of mouth swab samples. In total, the median yield and quality was determined in 714 individuals and the success rates in 378,480 genotypings of 915 individuals. The median yield of genomic DNA per mouth swab was 4.1 μg (range 0.1-42.2 μg) and was not reduced when mouth swabs were stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is collected per participant. Mouth swab samples showed in, respectively, 89% for 390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than 75%. A very low success rate of genotyping (0%-10%) was obtained for 3.2% of the 915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth swab samples showed a genotyping success rate lower than 75% (range 58%-71 %) using SNPs. Our results show that mouth swabs can be easily collected, stored by our conditions for months prior to DNA extraction and result in high yield and high-quality DNA appropriate for genotyping with high success rate including whole genome searches using microsatellites or SNPs

Family based association analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism, Anxiety and Depression

We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression

Linkage analysis of smoking initiation and quantity in Dutch sibling pairs.

The heritability of smoking initiation (SI) and number of cigarettes smoked (NC) was determined in 3657 Dutch twin pairs. For SI a heritability of 36% was found and for NC of 51%. Both SI and NC were also significantly influenced by environmental factors shared by family members. The etiological factors that influence these traits partly overlap. Linkage analyses were performed on data of 536 DZ twins and siblings from 192 families, forming 592 sibling pairs. Results suggested QTLs on chromosome 6 (LOD=3.05) and chromosome 14 (LOD=1.66) for SI and on chromosome 3 (LOD=1.98) for NC. Strikingly, on chromosome 10 a peak was found in the same region for both SI (LOD=1.92) and for NC (LOD=2.29) which may partly explain the overlapping etiological factors for SI and N

Both low circulating insulin-like growth factor-1 and high-density lipoprotein cholesterol are associated with hair loss in middle-aged women.

YesBackground: Multiple biomarkers have been associated with hair loss in women, but studies showed inconsistent results. Objective: We investigated the association between markers of cardiovascular disease risk (e.g., serum lipid levels and hypertension) and aging (e.g., 25-hydroxyvitamin D and insulin-like growth factor) with hair loss in a population of middle-aged women. Methods: In a random subgroup of 323 middle-aged women (mean age: 61.5 years) from the Leiden Longevity Study, hair loss was graded by three assessors using the Sinclair scale; women with a mean score higher than 1.5 were classified as cases with hair loss. Results: Every standard deviation increase in HDL cholesterol was associated with a 0.65 times lower risk (95% confidence interval [CI]: 0.46–0.91) of hair loss; for IGF-1 the risk was 0.68 times lower (95% CI: 0.48–0.97) per standard deviation increase, independent of the other studied variables. Women with both IGF-1 and HDL cholesterol levels below the median of the study population had a 3.47 times higher risk (95% CI: 1.30–9.25) of having hair loss. Limitations: The observational setting limits causal inference of the findings. Conclusion: Low HDL cholesterol and IGF-1 were associated with a higher risk of hair loss in women.This study was funded by the Innovation Oriented Research Program on Genomics (SenterNovem; IGE01014 and IGE5007), the Centre for Medical Systems Biology (CMSB), the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (05040202 and 050-060-810, NCHA), Unilever PLC and the European Union-funded Network of Excellence Lifespan (FP6 036894)

Genetic influences on disordered eating behaviour are largely independent of body mass index.

Objective: Prior studies suggest eating disorders and related characteristics are moderately to substantially heritable. We are interested in identifying the genes underlying disordered eating behaviour (DEB), and want to know how much of the genetic influence underlying DEB is attributable to genetic influences on body mass index (BMI). Method: Bivariate analyses were performed, in adolescent twins and siblings, to estimate the genetic and environmental contributions for DEB, BMI, and their overlap. Results: Shared genetic risk factors explained the overlap between BMI and DEB (genetic correlation was 0.43 in women, 0.51 in men). DEB was highly heritable in women (

Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study

SummaryObjectiveTo assess the relationship of biochemical markers and radiographic signs of osteoarthritis (ROA) in the subjects with symptomatic osteoarthritis (OA) at multiple sites of the Genetics osteoARthritis and Progression (GARP) study.MethodsWe have measured eight biochemical markers, representing tissue turnover of cartilage, bone, synovium, and inflammation. ROA was assessed in the knees, hips, hands, vertebral facet joints and spinal disc degeneration (DD) by using the Kellgren score. A proportionate score was subsequently made for each joint location based on the number of joints with ROA. Principal component and linear mixed model analyses were applied to analyze the data.ResultsThree different clusters of markers were identified that may reflect different pathophysiological processes of OA. The first component appeared to be reflected by structural markers of cartilage and bone turnover and associated especially in subjects with hip ROA. The second component was reflected by a marker of inflammation and was associated with knee ROA, high Western Ontario and McMaster Universities (WOMAC) scores and body mass index (BMI). The third component included markers of cartilage turnover and was associated with ROA at hands, spine as well as age. High familial aggregation was observed for serum cartilage oligomeric matrix protein (S-COMP) (70%) and serum N-propeptide of collagen type IIA (S-PIIANP) (62%).ConclusionUsing a large well-characterized study and eight biochemical markers, we were able to observe three components that may reflect different molecular mechanisms (bone, cartilage, synovium turnover and inflammation). Our data suggested that these components contribute differently to ROA at different joint sites