19 research outputs found
Multiple Measures of Adiposity Are Associated with Mean Leukocyte Telomere Length in the Northern Finland Birth Cohort 1966
No full textStudies of leukocyte telomere length (LTL) and adiposity have produced conflicting results, and the relationship between body mass index (BMI) and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i) childhood growth measures (BMI and age at adiposity rebound (AR)); ii) change in BMI from childhood to adulthood and iii) adult BMI, waist-to-hip ratio (WHR), body adiposity index (BAI). Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041). Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively) and women (P = 0.029 and P = 0.008, respectively), and BAI in women (P = 0.021) were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008). We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing
A neurobiological pathway to smoking in adolescence : TTC12-ANKK1-DRD2 variants and reward response
No full textThe TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10−4) and higher plasma cotinine levels (p = 7.0 × 10−5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.</p
Depression mediates the relationship between alexithymia and obesity in the Northern Finland Birth Cohort 1966 (NFBC1966)
No full textAbstract
Background:
The fact that a complex relationship exists between alexithymia and body mass index (BMI) is well established, but the underlying mechanisms remain poorly understood. Here, we explore the relationship between alexithymia and depressive symptoms in relation to adiposity measures, including the direct and indirect effect of alexithymia and depressive symptoms on obesity over a 15-year time-period, in the Northern Finland Birth Cohort 1966 (NFBC1966).
Methods:
The study included individuals from the Northern Finland Birth Cohort 1966 (NFBC1966) who had available data for adiposity measures (body mass index and waist-to-hip ratio), alexithymia (measured by the 20-Item Toronto Alexithymia Scale: TAS-20), depressive symptoms (measured by the 13-item depression subscale of Hopkins Symptom Checklist: HSCL-13) at age of 31 years (n = 4773) and 46 years (n = 4431). Pearson's (r) correlation, and multiple linear regression were used to investigate the relationships between alexithymia, depressive symptoms, and adiposity measures. The potential mediating role of depressive symptoms was examined via Hayes' procedure (PROCESS).
Results:
Positive correlations were confirmed between adiposity measures (BMI and WHR) and the TAS-20 score (and its subscale), but not between obesity and HSCL-13 score. The strongest correlation was between the DIF (difficulty identifying feelings) subscale of the TAS-20 and HSCL-13 at both time points (31 y: r(3013) = 0.41, p < 0.01, 46 y: r(3013) = 0.43, p < 0.01). Depressive symptoms completely (z = 2.55 (±0.00003), p = 0.01) and partly (z = 2.16 (±0.0001), p = 0.03) mediated the alexithymia-obesity relationship over the 15-year time-period.
Limitations:
Other psychological and environmental factors such as interoception, dietary intake and physical activities may also play a role as a potential mediating factor in alexithymia-obesity relationship.
Conclusions:
Our findings provide additional insights of theoretical framework of depressive symptoms mediation effect in the relationship between alexithymia and obesity. Alexithymia and depression should, therefore, be considered in the design of future clinical obesity research.Abstract
Background:
The fact that a complex relationship exists between alexithymia and body mass index (BMI) is well established, but the underlying mechanisms remain poorly understood. Here, we explore the relationship between alexithymia and depressive symptoms in relation to adiposity measures, including the direct and indirect effect of alexithymia and depressive symptoms on obesity over a 15-year time-period, in the Northern Finland Birth Cohort 1966 (NFBC1966).
Methods:
The study included individuals from the Northern Finland Birth Cohort 1966 (NFBC1966) who had available data for adiposity measures (body mass index and waist-to-hip ratio), alexithymia (measured by the 20-Item Toronto Alexithymia Scale: TAS-20), depressive symptoms (measured by the 13-item depression subscale of Hopkins Symptom Checklist: HSCL-13) at age of 31 years (n = 4773) and 46 years (n = 4431). Pearson's (r) correlation, and multiple linear regression were used to investigate the relationships between alexithymia, depressive symptoms, and adiposity measures. The potential mediating role of depressive symptoms was examined via Hayes' procedure (PROCESS).
Results:
Positive correlations were confirmed between adiposity measures (BMI and WHR) and the TAS-20 score (and its subscale), but not between obesity and HSCL-13 score. The strongest correlation was between the DIF (difficulty identifying feelings) subscale of the TAS-20 and HSCL-13 at both time points (31 y: r(3013) = 0.41, p < 0.01, 46 y: r(3013) = 0.43, p < 0.01). Depressive symptoms completely (z = 2.55 (±0.00003), p = 0.01) and partly (z = 2.16 (±0.0001), p = 0.03) mediated the alexithymia-obesity relationship over the 15-year time-period.
Limitations:
Other psychological and environmental factors such as interoception, dietary intake and physical activities may also play a role as a potential mediating factor in alexithymia-obesity relationship.
Conclusions:
Our findings provide additional insights of theoretical framework of depressive symptoms mediation effect in the relationship between alexithymia and obesity. Alexithymia and depression should, therefore, be considered in the design of future clinical obesity research
Chromosome 19p13.3 deletion in a patient with macrocephaly, obesity, mental retardation, and behavior problems
No full textAn Allele of the Interleukin-1 Receptor Antagonist as a Genetic Severity Factor in Alopecia Areata
No full text
The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases
No full textThe SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
Novel association approach for variable number tandem repeats (vntrs) identifies Dock5 as a susceptibility gene for severe obesity
No full textVariable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (Pempirical = 8.9 × 10-8 and P = 3.1 × 10-3, respectively) which we estimate explains ~0.8% of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46% of the variance (Pcombined = 1.6 × 10-3). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P = 0.027) and both VNTRs (Pempirical = 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies
Inferring combined CNV/SNP haplotypes from genotype data
No full textMotivation: Copy number variations (CNVs) are increasingly recognized as an substantial source of individual genetic variation, and hence there is a growing interest in investigating the evolutionary history of CNVs as well as their impact on complex disease susceptibility. CNV/SNP haplotypes are critical for this research, but although many methods have been proposed for inferring integer copy number, few have been designed for inferring CNV haplotypic phase and none of these are applicable at genome-wide scale. Here, we present a method for inferring missing CNV genotypes, predicting CNV allelic configuration and for inferring CNV haplotypic phase from SNP/CNV genotype data. Our method, implemented in the software polyHap v2.0, is based on a hidden Markov model, which models the joint haplotype structure between CNVs and SNPs. Thus, haplotypic phase of CNVs and SNPs are inferred simultaneously. A sampling algorithm is employed to obtain a measure of confidence/credibility of each estimate. Results: We generated diploid phase-known CNV-SNP genotype datasets by pairing male X chromosome CNV-SNP haplotypes. We show that polyHap provides accurate estimates of missing CNV genotypes, allelic configuration and CNV haplotypic phase on these datasets. We applied our method to a non-simulated dataset-a region on Chromosome 2 encompassing a short deletion. The results confirm that polyHap's accuracy extends to real-life datasets
Body composition of the host influences dendritic cell phenotype in patients treated for colorectal cancer
No full textDendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = −0.46, p = 0.03.) and with CD83 [all DCs (r = −0.63; p = 0.01) and myeloid DCs (r = −0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC
