scholarly journals Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study

2020 ◽  
Author(s):  
Frauke Beyer ◽  
Rui Zhang ◽  
Markus Scholz ◽  
Kerstin Wirkner ◽  
Markus Loeffler ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Genetic Variants ◽  
Structural Connectivity ◽  
Population Based ◽  
Reward Processing ◽  
Clustering Coefficient ◽  
Graph Metrics ◽  
Wide Range ◽  
Reward Network ◽  
Connectivity Strength

Abstract Background Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. Methods We analyzed 347 participants (age range: 20–59 years, BMI range: 17–38 kg/m2) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. Results Higher BMI was significantly associated with lower connectivity strength for number of streamlines (β = −0.0025, 95%—C.I.: [−0.004, −0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (β = −0.0009, 95%—C.I. [−0.0016, −0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. Conclusions Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

scholarly journals Higher BMI, but not obesity-related genetic polymorphisms, correlates with reduced structural connectivity of the reward network

2020 ◽  
Author(s):  
Frauke Beyer ◽  
Rui Zhang ◽  
Markus Scholz ◽  
Kerstin Wirkner ◽  
Markus Loeffler ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Dopamine D2 Receptor ◽  
Structural Connectivity ◽  
Reward Processing ◽  
Clustering Coefficient ◽  
Future Research ◽  
Graph Metrics ◽  
Reward Network ◽  
The Brain ◽  
Connectivity Strength

BackgroundObesity is of complex origin, involving genetic and neurobehavioral factors. Most consistently, polymorphisms in the fat-and-obesity associated gene (FTO) may increase the risk for developing obesity by modulating dopaminergic signaling in the brain. Dopamine-dependent behaviors, such as reward processing, are crucial for eating behavior and are altered in obesity. Yet, few studies have investigated the association of obesity, related genetic variants and structural connectivity of the dopaminergic reward network.MethodsWe analyzed 378 participants (age range: 20 – 59 years, BMI range: 17 – 38 kg/m2) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a micro-array. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 Tesla using deterministic tractography of Freesurfer-de-rived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions, normalized for global connectivity. We applied linear regression models to test the association of BMI, risk alleles of both variants and reward network connectivity.ResultsHigher BMI was significantly associated with reduced connectivity strength for fractional anisotropy (β= −0.0011, 95%-C.I. [−0.0019, −0.0003], p= 0.0062) and number of streamlines (β = −0.0026, 95%-C.I.:[−0.004,−0.0009], p= 0.0024), but not clustering coefficient. Strongest associations were found for right accumbens, right lateral orbitofrontal cortex and left putamen. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F=7.9, p<0.001). None of the genetic variants was associated with reward network structural connectivity.ConclusionsHere, we provide evidence that higher BMI correlates with reduced reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not find any association of variants in FTO or near DRD2 receptor and reward network structural connectivity, indicating that the genetic influence of these variants is small or non-existent. Future research should investigate the behavioral implications of structural connectivity differences in the fronto-striatal network and incorporate larger sample sizes with longitudinal designs in order to gain further insight into the genetic determinants of obesity in the brain.

scholarly journals Multimodal neuroimaging and suicidality in a US population-based sample of school-aged children

2019 ◽  
Author(s):  
Pablo Vidal-Ribas ◽  
Delfina Janiri ◽  
Gaelle E. Doucet ◽  
Narun Pornpattananangkul ◽  
Dylan M. Nielson ◽  
...  
Keyword(s):  
Large Scale ◽  
Population Based ◽  
Reward Processing ◽  
Left Bank ◽  
Multimodal Neuroimaging ◽  
Available N ◽  
Predictive Values ◽  
School Aged Children ◽  
Wide Range ◽  
And Task

AbstractImportanceSuicide deaths and suicidality are considered a public health emergency, yet their brain underpinnings remain elusive.ObjectiveTo examine individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates of suicidality in a US population-based sample of school-aged children.DesignCross-sectional analysis of the first wave of data from the Adolescent Brain Cognitive Development studySettingMulticenter population-based studyParticipantsChildren aged 9-10 years from unreferred, community samples with suicidality data available (n=7,994). Following quality control, we examined structural magnetic resonance imaging (sMRI) (n=6,238), resting state functional MRI (rs-fMRI) (n=4,134), and task-based fMRI (range n=4,075 to 4,608).ExposureLifetime suicidality, defined as suicidal ideation, plans and attempts reported by children or/and caregivers.Main Outcomes and MeasuresMultimodal neuroimaging analyses examined differences with Welch’s t-test and Equivalence Tests, with observed effect sizes (ES, Cohen’s d) and their 90% confidence interval (CI) < |0.15|. Predictive values were examined using the area under precision-recall curves (AUPRC). Measures included, cortical volume and thickness, large-scale network connectivity and task-based MRI of reward processing, inhibitory control and working memory.ResultsAmong the 7,994 unrelated children (3,757 females [47.0%]), those will lifetime suicidality based on children (n=684 [8.6%]; 276 females [40.4%]), caregiver (n=654 [8.2%]; 233 females [35.6%]) or concordant reports (n=198 [2.5%]; 67 females [33.8%]), presented higher levels of social adversity and psychopathology on themselves and their caregivers compared to never-suicidal children (n=6,854 [85.7%]; 3,315 females [48.3%]). A wide range of brain areas was associated with suicidality, but only one test (0.06%) survived statistical correction: children with caregiver-reported suicidality had a thinner left bank of the superior temporal sulcus compared to never-suicidal children (ES=-0.17, 95%CI -0.26, -0.08, pFDR=0.019). Based on the prespecified bounds of |0.15|, ∼48% of the group mean differences for child-reported suicidality comparisons and a ∼22% for parent-reported suicidality comparisons were considered equivalent. All observed ES were relatively small (d≤|0.20|) and with low predictive value (AUPRC≤0.10).Conclusion and RelevanceUsing commonly-applied neuroimaging measures, we were unable to find a discrete brain signature related to suicidality in youth. There is a great need for improved approaches to the neurobiology of suicide.

Strong Association between Serotonin Transporter 5-HTTVNTR Variant and Psychoactive Substance (Nicotine) Use in the Turkish Cypriot Population

2020 ◽  
Vol 21 (6) ◽  
pp. 466-470
Author(s):  
Emine Kandemis ◽  
Gulten Tuncel ◽  
Ozen Asut ◽  
Sehime G. Temel ◽  
Mahmut C. Ergoren
Keyword(s):  
Serotonin Transporter ◽  
Association Studies ◽  
Strong Association ◽  
Smoking Behavior ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Genotype Distribution ◽  
Psychological Traits ◽  
Wide Range ◽  
Turkish Cypriot

Background: The use of psychoactive substances is one of the most dangerous social problems worldwide. Nicotine dependence results from the interaction between neurobiological, environmental and genetic factors. Serotonin is a neurotransmitter that has a wide range of central nervous system activities. The serotonin transporter gene has been previously linked to psychological traits. Objective: A variable number of tandem repeats within the serotonin transporter-linked polymorphic gene region are believed to alter the transcriptional efficiency of the 5-HTT gene. Therefore, we aimed to investigate the association between this polymorphic site and smoking behavior in the Turkish Cypriot population. Methods: A total of 259 (100 smokers, 100 non-smokers and 59 ex-smokers) Turkish Cypriots were included in this population-based cross-sectional study. Genomic DNA was extracted from peripheral blood samples and the 5-HTTVNTR2 polymorphisms were determined by the PCR-RFLP. Results: The allelic frequency and genotype distribution results of this study showed a strong association (P<0.0001) between smokers and non-smokers. No statistical significance was found between non-smokers and ex-smokers. Conclusion: This is the first genetic epidemiology study to investigate the allelic frequencies of 5-HTTVNTR2 polymorphisms associated with smoking behavior in the Turkish Cypriot population. Based on the results of this study, genome-wide association studies should be designed for preventive medicine in this population.

scholarly journals Case–Parent Trio Studies in Cleft Lip and Palate

2020 ◽  
Vol 07 (03) ◽  
pp. 075-079
Author(s):  
Mahamad Irfanulla Khan ◽  
Prashanth CS
Keyword(s):  
Genetic Variants ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Geographical Location ◽  
Genetic Association Studies ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Family Based ◽  
Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

scholarly journals Genetic, lifestyle, and health-related characteristics of adults without celiac disease who follow a gluten-free diet: a population-based study of 124,447 participants

2020 ◽  
Author(s):  
Thomas J Littlejohns ◽  
Amanda Y Chong ◽  
Naomi E Allen ◽  
Matthew Arnold ◽  
Kathryn E Bradbury ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Gluten Free Diet ◽  
Hospital Inpatient ◽  
Gluten Free ◽  
A Genome ◽  
Wide Range ◽  
Health Related ◽  
Reported Health

ABSTRACT Background The number of gluten-free diet followers without celiac disease (CD) is increasing. However, little is known about the characteristics of these individuals. Objectives We address this issue by investigating a wide range of genetic and phenotypic characteristics in association with following a gluten-free diet. Methods The cross-sectional association between lifestyle and health-related characteristics and following a gluten-free diet was investigated in 124,447 women and men aged 40–69 y from the population-based UK Biobank study. A genome-wide association study (GWAS) of following a gluten-free diet was performed. Results A total of 1776 (1.4%) participants reported following a gluten-free diet. Gluten-free diet followers were more likely to be women, nonwhite, highly educated, living in more socioeconomically deprived areas, former smokers, have lost weight in the past year, have poorer self-reported health, and have made dietary changes as a result of illness. Conversely, these individuals were less likely to consume alcohol daily, be overweight or obese, have hypertension, or use cholesterol-lowering medication. Participants with hospital inpatient diagnosed blood and immune mechanism disorders (OR: 1.62; 95% CI: 1.18, 2.21) and non-CD digestive system diseases (OR: 1.58; 95% CI: 1.42, 1.77) were more likely to follow a gluten-free diet. The GWAS demonstrated that no genetic variants were associated with being a gluten-free diet follower. Conclusions Gluten-free diet followers have a better cardiovascular risk profile than non-gluten-free diet followers but poorer self-reported health and a higher prevalence of blood and immune disorders and digestive conditions. Reasons for following a gluten-free diet warrant further investigation.

Registry of Adolescent and Young Adult Twins in the Tokyo Area

2006 ◽  
Vol 9 (6) ◽  
pp. 811-816 ◽  
Author(s):  
Chizuru Shikishima ◽  
Juko Ando ◽  
Yutaka Ono ◽  
Tatsushi Toda ◽  
Kimio Yoshimura
Keyword(s):  
Behavior Genetics ◽  
Human Genetics ◽  
Population Based ◽  
Adolescent And Young Adult ◽  
Multiple Traits ◽  
Psychological Traits ◽  
Physical Measurements ◽  
Wide Range ◽  
Psychology Perspective ◽  
Adult Twins

AbstractSince established in 1998, the Keio Twin Project (KTP) has been dedicated to investigating genetic and environmental sources contributing to human psychological traits in adolescence and young adulthood. A population-based twin registry was constructed by the KTP through the use of official residential records in the Tokyo area, and to date requests to participate in our research have generated 1040 pairs of twins and triplets of age 14 to 30, forming one of the largest twin registries in Asia. Our comprehensive datasets, obtained through questionnaires, performance tests, and physical measurements, cover a wide range of human traits: personality, psychiatry, mental health, sociality, cognition, and physical index. Demographic variables and environment of upbringing are also sought by twins and by some parents. This extensive information allows us to clarify the genetic and environmental overlap across multiple traits as well as specificities unique to single traits. Adding an evolutionary psychology perspective to the behavior genetics framework is currently being attempted in order to develop a grand theory of human genetics.

scholarly journals Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants

Diabetologia ◽  
2021 ◽  
Author(s):  
Ziyi Zhou ◽  
John Macpherson ◽  
Stuart R. Gray ◽  
Jason M. R. Gill ◽  
Paul Welsh ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Respiratory Diseases ◽  
Population Based ◽  
Incident Diabetes ◽  
Uk Biobank ◽  
Metabolically Healthy Obesity ◽  
Wide Range ◽  
Metabolically Healthy

Abstract Aims/hypothesis People with obesity and a normal metabolic profile are sometimes referred to as having ‘metabolically healthy obesity’ (MHO). However, whether this group of individuals are actually ‘healthy’ is uncertain. This study aims to examine the associations of MHO with a wide range of obesity-related outcomes. Methods This is a population-based prospective cohort study of 381,363 UK Biobank participants with a median follow-up of 11.2 years. MHO was defined as having a BMI ≥ 30 kg/m2 and at least four of the six metabolically healthy criteria. Outcomes included incident diabetes and incident and fatal atherosclerotic CVD (ASCVD), heart failure (HF) and respiratory diseases. Results Compared with people who were not obese at baseline, those with MHO had higher incident HF (HR 1.60; 95% CI 1.45, 1.75) and respiratory disease (HR 1.20; 95% CI 1.16, 1.25) rates, but not higher ASCVD. The associations of MHO were generally weaker for fatal outcomes and only significant for all-cause (HR 1.12; 95% CI 1.04, 1.21) and HF mortality rates (HR 1.44; 95% CI 1.09, 1.89). However, when compared with people who were metabolically healthy without obesity, participants with MHO had higher rates of incident diabetes (HR 4.32; 95% CI 3.83, 4.89), ASCVD (HR 1.18; 95% CI 1.10, 1.27), HF (HR 1.76; 95% CI 1.61, 1.92), respiratory diseases (HR 1.28; 95% CI 1.24, 1.33) and all-cause mortality (HR 1.22; 95% CI 1.14, 1.31). The results with a 5 year landmark analysis were similar. Conclusions/interpretation Weight management should be recommended to all people with obesity, irrespective of their metabolic status, to lower risk of diabetes, ASCVD, HF and respiratory diseases. The term ‘MHO’ should be avoided as it is misleading and different strategies for risk stratification should be explored. Graphical abstract

scholarly journals A Model for Analysing the Collective Dynamic Behaviour and Characterising the Exploitation of Population-Based Algorithms

2014 ◽  
Vol 22 (1) ◽  
pp. 159-188 ◽  
Author(s):  
Mikdam Turkey ◽  
Riccardo Poli
Keyword(s):  
Population Dynamics ◽  
Dynamic Behaviour ◽  
Fitness Landscape ◽  
Population Based ◽  
Levels Of Abstraction ◽  
Collective Dynamic ◽  
Model Studies ◽  
Proposed Model ◽  
Wide Range ◽  
Multiple Levels

Several previous studies have focused on modelling and analysing the collective dynamic behaviour of population-based algorithms. However, an empirical approach for identifying and characterising such a behaviour is surprisingly lacking. In this paper, we present a new model to capture this collective behaviour, and to extract and quantify features associated with it. The proposed model studies the topological distribution of an algorithm's activity from both a genotypic and a phenotypic perspective, and represents population dynamics using multiple levels of abstraction. The model can have different instantiations. Here it has been implemented using a modified version of self-organising maps. These are used to represent and track the population motion in the fitness landscape as the algorithm operates on solving a problem. Based on this model, we developed a set of features that characterise the population's collective dynamic behaviour. By analysing them and revealing their dependency on fitness distributions, we were then able to define an indicator of the exploitation behaviour of an algorithm. This is an entropy-based measure that assesses the dependency on fitness distributions of different features of population dynamics. To test the proposed measures, evolutionary algorithms with different crossover operators, selection pressure levels and population handling techniques have been examined, which lead populations to exhibit a wide range of exploitation-exploration behaviours.

FRAILTY AND SARCOPAENIA TRIALS IN PRIMARY CARE – IDENTIFYING AND OVERCOMING KEY BARRIERS TO SUCCESSFUL CLINICIAN PARTICIPATION

2015 ◽  
pp. 1-2
Author(s):  
A. SINCLAIR
Keyword(s):  
Primary Care ◽  
Target Population ◽  
Population Based ◽  
Care Staff ◽  
Long Term Conditions ◽  
Primary Care Research ◽  
Wide Range ◽  
Primary Care Practitioners ◽  
Primary Care Staff

Primary care research involving older people brings together a wide range of primary care practitioners. Key areas of activity include: health promotion, disease prevention, screening and early diagnosis, as well as the management of common and long-term conditions such as frailty and sarcopaenia which are under-researched domains of health in this setting. Few interventional studies have identified frail or sarcopaenic patients as the target population based on recent definitions of either condition. Several barriers to successful research in the primary care area exist and overcoming such barriers is not straightforward but involves a multidimensional approach that attempts to enhance the confidence and opportunity to engage in research of primary care staff and the consideration of factors that allow external leads of research to coordinate their programme.

Sign in / Sign up

Export Citation Format

Share Document