scholarly journals Evidence of genetic overlap between circadian preference and brain white matter microstructure

2020 ◽  
Author(s):  
Luis M. García-Marín ◽  
Sarael Alcauter ◽  
Adrian I. Campos ◽  
Aoibhe Mulcahy ◽  
Pik-Fang Kho ◽  
...  
Keyword(s):  
White Matter ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Study Objective ◽  
Brain White Matter ◽  
White Matter Microstructure ◽  
Genetic Overlap ◽  
Circadian Preference

AbstractStudy objectivePrevious neuroimaging studies have highlighted differences in white matter microstructure among individuals with different chronotypes, but it is unclear whether those differences are due to genetic or environmental factors.MethodsHere we leverage summary statistics from recent large-scale genome-wide association studies (GWAS) of chronotype and diffusion tensor imaging (DTI) measures to examine the genetic overlap and infer causal relationships between these traits.ResultsWe identified 29 significant pairwise genetic correlations, of which 13 also had evidence for a causal association. Negative genetic correlations were identified between chronotype and brain-wide mean, axial and radial diffusivities. When exploring individual tracts, ten negative genetic correlations were observed with mean diffusivities, 10 with axial diffusivities, 4 with radial diffusivities and 2 with mode of anisotropy. We found evidence for a possible causal association of chronotype with white matter microstructure in individual tracts including the posterior limb and retrolenticular part of the internal capsule; the genu and splenium of the corpus callosum and the posterior, superior and anterior regions of the corona radiata.ConclusionsOur results suggest that eveningness is associated with variation in tract-specific white matter microstructure and, for an evening person, increases in axial and / or radial diffusivities may influence a higher mean diffusivity. These findings add to our understanding of circadian preference and its relationship with the brain, providing new perspectives on the genetic neurological underpinnings of chronotype’s role in health and disease.Statement of SignificanceSleep is essential for a healthy brain function, particularly for neural organization and brain structure development. Individual chronotype differences have been associated with depression, schizophrenia, diabetes and obesity, among other conditions. Investigating the shared genetic aetiology between chronotype and white matter microstructure is essential to understand the neurological basis of individual variation in chronotype. In the present study, we show that tract-specific white matter microstructure is genetically correlated and causally associated with chronotype.

scholarly journals Evidence of Genetic Overlap Between Circadian Preference and Brain White Matter Microstructure

2021 ◽  
Vol 24 (1) ◽  
pp. 1-6
Author(s):  
Luis M. García-Marín ◽  
Sarael Alcauter ◽  
Adrian I. Campos ◽  
Aoibhe Mulcahy ◽  
Pik-Fang Kho ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Genetic Correlations ◽  
Mean Diffusivity ◽  
Causal Association ◽  
Posterior Limb ◽  
Brain White Matter ◽  
White Matter Microstructure ◽  
Genetic Overlap ◽  
Circadian Preference

AbstractSeveral neuroimaging studies have reported associations between brain white matter microstructure and chronotype. However, it is unclear whether those phenotypic relationships are causal or underlined by genetic factors. In the present study, we use genetic data to examine the genetic overlap and infer causal relationships between chronotype and diffusion tensor imaging (DTI) measures. We identify 29 significant pairwise genetic correlations, of which 13 also show evidence for a causal association. Genetic correlations were identified between chronotype and brain-wide mean, axial and radial diffusivities. When exploring individual tracts, 10 genetic correlations were observed with mean diffusivity, 10 with axial diffusivity, 4 with radial diffusivity and 2 with mode of anisotropy. We found evidence for a possible causal association of eveningness with white matter microstructure measures in individual tracts including the posterior limb and the retrolenticular part of the internal capsule; the genu and splenium of the corpus callosum and the posterior, superior and anterior regions of the corona radiata. Our findings contribute to the understanding of how genes influence circadian preference and brain white matter and provide a new avenue for investigating the role of chronotype in health and disease.

scholarly journals Genome-wide discovered psychosis-risk gene ZNF804A impacts on white matter microstructure in health, schizophrenia and bipolar disorder

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1570 ◽  
Author(s):  
Emma-Jane Mallas ◽  
Francesco Carletti ◽  
Christopher A. Chaddock ◽  
James Woolley ◽  
Marco M. Picchioni ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Diffusion Tensor ◽  
Clinical Sample ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Risk Variant ◽  
White Matter Microstructure ◽  
Genome Wide ◽  
The Impact

Background.Schizophrenia (SZ) and bipolar disorder (BD) have both been associated with reduced microstructural white matter integrity using, as a proxy, fractional anisotropy (FA) detected using diffusion tensor imaging (DTI). Genetic susceptibility for both illnesses has also been positively correlated in recent genome-wide association studies with allele A (adenine) of single nucleotide polymorphism (SNP) rs1344706 of the ZNF804A gene. However, little is known about how the genomic linkage disequilibrium region tagged by this SNP impacts on the brain to increase risk for psychosis. This study aimed to assess the impact of this risk variant on FA in patients with SZ, in those with BD and in healthy controls.Methods.230 individuals were genotyped for the rs1344706 SNP and underwent DTI. We used tract-based spatial statistics (TBSS) followed by an analysis of variance, with threshold-free cluster enhancement (TFCE), to assess underlying effects of genotype, diagnosis and their interaction, on FA.Results.As predicted, statistically significant reductions in FA across a widely distributed brain network (p< 0.05, TFCE-corrected) were positively associated both with a diagnosis of SZ or BD and with the double (homozygous) presence of the ZNF804A rs1344706 risk variant (A). The main effect of genotype was medium (d= 0.48 in a 44,054-voxel cluster) and the effect in the SZ group alone was large (d= 1.01 in a 51,260-voxel cluster), with no significant effects in BD or controls, in isolation. No areas under a significant diagnosis by genotype interaction were found.Discussion.We provide the first evidence in a predominantly Caucasian clinical sample, of an association betweenZNF804Ars1344706 A-homozygosity and reduced FA, both irrespective of diagnosis and particularly in SZ (in overlapping brain areas). This suggests that the previously observed involvement of this genomic region in psychosis susceptibility, and in impaired functional connectivity, may be conferred through it inducing abnormalities in white matter microstructure.

Genetics

2018 ◽  
Author(s):  
Carol Kan ◽  
Ma-Li Wong
Keyword(s):  
Complex Traits ◽  
Association Studies ◽  
Genetic Correlations ◽  
Twin Studies ◽  
Epidemiological Studies ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
Small Magnitude ◽  
Gene Environment ◽  
Genetic Overlap

An association between type 2 diabetes mellitus (T2DM) and depression has been reported in epidemiological studies. Finding a genetic overlap between T2DM and depression will provide evidence to support a common biological pathway to both disorders. Genetic correlations observed from twin studies indicate that a small magnitude of the variance in liability can be attributed to genetic factors. However, no genetic overlap has been observed between T2DM and depression in genome-wide association studies using both the polygenic score and the linkage disequilibrium score regression approaches. Clarifying the shared heritability between these two complex traits is an important next step towards better therapy and treatment. Another area that needs to be explored is gene–environment interaction, since genotypes can affect an individual’s responses to the environment and environment can differentially affect genotypes expression.

scholarly journals A genetic perspective on the relationship between eudaimonic –and hedonic well-being

2018 ◽  
Author(s):  
B.M.L. Baselmans ◽  
M. Bartels
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Molecular Genetic ◽  
Genetic Correlations ◽  
Well Being ◽  
Phenotypic Correlation ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Molecular Genetic Data ◽  
Genetic Overlap

AbstractWhether hedonism or eudaimonism are two distinguishable forms of well-being is a topic of ongoing debate. To shed light on the relation between the two, large-scale available molecular genetic data were leveraged to gain more insight into the genetic architecture of the overlap between hedonic and eudaimonic well-being. Hence, we conducted the first genome-wide association studies (GWAS) of eudaimonic well-being (N = ∼108K) and linked it to a GWAS of hedonic well-being (N = ∼ 222K). We identified the first two genome-wide significant independent loci for eudaimonic well-being and 6 independent loci for hedonic well-being. Joint analyses revealed a moderate phenotypic correlation (r = 0.53), but a high genetic correlation (rg = 0.78) between eudaimonic and hedonic well-being. For both traits we identified enrichment in the frontal cortex -and cingulate cortex as well as the cerebellum to be top ranked. Bi-directional Mendelian Randomization analyses using two-sample MR indicated some evidence for a causal relationship from hedonic well-being to eudaimonic well-being whereas no evidence was found for the reverse. Additionally, genetic correlations patterns with a range of positive and negative related phenotypes were largely similar for hedonic –and eudaimonic well-being. Our results reveal a large genetic overlap between hedonism and eudaimonism.

scholarly journals Genetic overlap between Parkinson disease and inflammatory bowel disease

2022 ◽  
Author(s):  
Xiaoying Kang ◽  
Alexander Ploner ◽  
Yunzhang Wang ◽  
Jonas F Ludvigsson ◽  
Dylan M Williams ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Parkinson Disease ◽  
Bowel Disease ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
High Definition ◽  
Genetic Overlap ◽  
Common Etiology ◽  
Inflammatory Bowel

Importance Parkinson disease (PD) and inflammatory bowel disease (IBD) have been associated, implying shared pathophysiology. Characterizing genetic pleiotropy between the two conditions aids the exploration of common etiology. Objective To estimate the genetic correlation between PD and IBD and to identify specific loci influencing both conditions. Design Genetic study with applications of high definition likelihood and conditional false discovery rate (FDR) framework. Setting The study was based on summary statistics of genome-wide association studies (GWAS). Participants The PD GWAS comprised 37,688 cases and 981,372 controls, and the IBD GWAS included 25,042 cases and 34,915 controls. Participants were of mixed ethnicity. Exposures None. Main Outcomes and Measures The main outcomes were a set of single nucleotide polymorphisms (SNPs) identified by conditional FDR analysis as jointly associated with PD and IBD. Results Weak but statistically significant genetic correlations were detected for PD with both Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of IBD. A total of 1333 SNPs in 28 genomic loci and 1915 SNPs in 22 loci were jointly associated with PD-CD and PD-UC, respectively, at conjunctional FDR under 0.01. The pleiotropic loci appeared distinctive for PD-CD and PD-UC, are mostly novel and comprise loci with either same or opposing genetic effects on the two phenotypes. Positional and eQTL mapping prioritized 316 PD-CD and 303 PD-UC genes, among which only <10% are differentially expressed in both colon and substantia nigra. The KEGG pathways enriched by all prioritized genes were highly concordant between PD-CD and PD-UC, with the majority being related to immune and/or autoimmune dysfunction. Conclusions and Relevance Overall, we found robust evidence for a genetic link between PD and each subtype of IBD. The identified genetic overlap is complex at the locus and gene levels, indicating the presence of both common etiology and antagonistic pleiotropy. At the functional level, our results highlighted a central role of host immunity and/or autoimmunity in the PD-IBD relationship.

scholarly journals Coupled Changes in Brain White Matter Microstructure and Fluid Intelligence in Later Life

2015 ◽  
Vol 35 (22) ◽  
pp. 8672-8682 ◽  
Author(s):  
Stuart J. Ritchie ◽  
Mark E. Bastin ◽  
Elliot M. Tucker-Drob ◽  
Susana Muñoz Maniega ◽  
Laura E. Engelhardt ◽  
...  
Keyword(s):  
White Matter ◽  
Fluid Intelligence ◽  
Later Life ◽  
Brain White Matter ◽  
White Matter Microstructure

scholarly journals Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours

2017 ◽  
Author(s):  
Jorien L. Treur ◽  
Mark Gibson ◽  
Amy E Taylor ◽  
Peter J Rogers ◽  
Marcus R Munafò
Keyword(s):  
Genetic Correlation ◽  
Sleep Duration ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genetic Correlations ◽  
Causal Effects ◽  
Genome Wide Association Studies ◽  
Caffeine Consumption ◽  
Insomnia Complaints

AbstractStudy Objectives:Higher caffeine consumption has been linked to poorer sleep and insomnia complaints. We investigated whether these observational associations are the result of genetic risk factors influencing both caffeine consumption and poorer sleep, and/or whether they reflect (possibly bidirectional) causal effects.Methods:Summary-level data were available from genome-wide association studies (GWAS) on caffeine consumption (n=91,462), sleep duration, and chronotype (i.e., being a ‘morning’ versus an ‘evening’ person) (both n=128,266), and insomnia complaints (n=113,006). Linkage disequilibrium (LD) score regression was used to calculate genetic correlations, reflecting the extent to which genetic variants influencing caffeine consumption and sleep behaviours overlap. Causal effects were tested with bidirectional, two-sample Mendelian randomization (MR), an instrumental variable approach that utilizes genetic variants robustly associated with an exposure variable as an instrument to test causal effects. Estimates from individual genetic variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods.Results:There was no clear evidence for genetic correlation between caffeine consumption and sleep duration (rg=0.000,p=0.998), chronotype (rg=0.086,p=0.192) or insomnia (rg=-0.034,p=0.700). Two-sample Mendelian randomization analyses did not support causal effects from caffeine consumption to sleep behaviours, or the other way around.Conclusions:We found no evidence in support of genetic correlation or causal effects between caffeine consumption and sleep. While caffeine may have acute effects on sleep when taken shortly before habitual bedtime, our findings suggest that a more sustained pattern of high caffeine consumption is likely associated with poorer sleep through shared environmental factors.

scholarly journals Genetic overlap between idiopathic pulmonary fibrosis and COVID−19

2021 ◽  
Author(s):  
Richard J Allen ◽  
Beatriz Guillen-Guio ◽  
Emma Croot ◽  
Luke M Kraven ◽  
Samuel Moss ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Biological Processes ◽  
Genetic Loci ◽  
Genome Wide ◽  
Genetic Overlap ◽  
Causal Variants ◽  
Shared Genetic

AbstractGenome-wide association studies (GWAS) of coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) have identified genetic loci associated with both traits, suggesting possible shared biological mechanisms. Using updated GWAS of COVID-19 and IPF, we evaluated the genetic overlap between these two diseases and identified four genetic loci (including one novel) with likely shared causal variants between severe COVID-19 and IPF. Although there was a positive genetic correlation between COVID-19 and IPF, two of these four shared genetic loci had an opposite direction of effect. IPF-associated genetic variants related to telomere dysfunction and spindle assembly showed no association with COVID-19 phenotypes. Together, these results suggest there are both shared and distinct biological processes driving IPF and severe COVID-19 phenotypes.

A systematic analysis of genetically regulated differences in gene expression and the role of co-expression networks across 16 psychiatric disorders and substance use phenotypes

2021 ◽  
Author(s):  
Zachary F Gerring ◽  
Jackson G Thorp ◽  
Eric R Gamazon ◽  
Eske M Derks
Keyword(s):  
Gene Expression ◽  
Mental Health ◽  
Substance Use ◽  
Prefrontal Cortex ◽  
Psychiatric Disorders ◽  
Developmental Disorders ◽  
Association Studies ◽  
Genetic Correlations ◽  
Autism Spectrum ◽  
Genome Wide Association Studies

ABSTRACTGenome-wide association studies (GWASs) have identified thousands of risk loci for many psychiatric and substance use phenotypes, however the biological consequences of these loci remain largely unknown. We performed a transcriptome-wide association study of 10 psychiatric disorders and 6 substance use phenotypes (collectively termed “mental health phenotypes”) using expression quantitative trait loci data from 532 prefrontal cortex samples. We estimated the correlation due to predicted genetically regulated expression between pairs of mental health phenotypes, and compared the results with the genetic correlations. We identified 1,645 genes with at least one significant trait association, comprising 2,176 significant associations across the 16 mental health phenotypes of which 572 (26%) are novel. Overall, the transcriptomic correlations for phenotype pairs were significantly higher than the respective genetic correlations. For example, attention deficit hyperactivity disorder and autism spectrum disorder, both childhood developmental disorders, showed a much higher transcriptomic correlation (r=0.84) than genetic correlation (r=0.35). Finally, we tested the enrichment of phenotype-associated genes in gene co-expression networks built from prefrontal cortex. Phenotype-associated genes were enriched in multiple gene co-expression modules and the implicated modules contained genes involved in mRNA splicing and glutamatergic receptors, among others. Together, our results highlight the utility of gene expression data in the understanding of functional gene mechanisms underlying psychiatric disorders and substance use phenotypes.

Sign in / Sign up

Export Citation Format

Share Document