scholarly journals Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Edith Hofer ◽  
◽  
Gennady V. Roshchupkin ◽  
Hieab H. H. Adams ◽  
Maria J. Knol ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Genetic Correlations ◽  
Brain Regions ◽  
Aging Research ◽  
Genomic Epidemiology ◽  
Discovery Sample ◽  
Genome Wide ◽  
Psychiatric Conditions ◽  
Development And Aging ◽  
The Uk

Abstract Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

scholarly journals Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium

2018 ◽  
Author(s):  
Edith Hofer ◽  
Gennady V. Roshchupkin ◽  
Hieab H. H. Adams ◽  
Maria J. Knol ◽  
Honghuang Lin ◽  
...  
Keyword(s):  
Surface Area ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Brain Regions ◽  
Aging Research ◽  
Genomic Epidemiology ◽  
Discovery Sample ◽  
Genome Wide ◽  
Development And Aging ◽  
Pathway Analyses

AbstractCortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

scholarly journals Genomic Influences on Self-Reported Childhood Maltreatment

2019 ◽  
Author(s):  
Shareefa Dalvie ◽  
Adam X. Maihofer ◽  
Jonathan R.I. Coleman ◽  
Bekh Bradley ◽  
Gerome Breen ◽  
...  
Keyword(s):  
Physical Health ◽  
Childhood Maltreatment ◽  
Large Scale ◽  
Genetic Relationships ◽  
Genetic Correlations ◽  
Discovery Sample ◽  
Treatment And Prevention ◽  
Genome Wide ◽  
Physical Disorders ◽  
The Uk

AbstractChildhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to 1) identify genetic variation associated with reported childhood maltreatment, 2) calculate the relevant SNP-based heritability estimates, and 3) quantify the genetic overlap of reported childhood maltreatment with mental and physical health-related phenotypes. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n=124,000) and a replication sample from the Psychiatric Genomics Consortium–posttraumatic stress disorder working group (PGC-PTSD) (n=26,290). Heritability estimations for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression (LDSR). Two genome-wide significant loci associated with childhood maltreatment, located on chromosomes 3p13 (rs142346759, beta=0.015, p=4.35×10−8, FOXP1) and 7q31.1 (rs10262462, beta=-0.016, p=3.24×10−8, FOXP2), were identified in the discovery dataset but were not replicated in the PGC-PTSD sample. SNP-based heritability for childhood maltreatment was estimated to be ∼6%. Childhood maltreatment was most significantly genetically correlated with depressive symptoms (rg=0.70, p=4.65×10−40). This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. FOXP genes could influence traits such as depression and thereby be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with various psychiatric disorders, may ultimately be useful in in developing targeted treatment and prevention strategies.

scholarly journals GWAS in 446,118 European adults identifies 78 genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

2018 ◽  
Author(s):  
Hassan S Dashti ◽  
Samuel E Jones ◽  
Andrew R Wood ◽  
Jacqueline M Lane ◽  
Vincent T. van Hees ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Brain Regions ◽  
Causal Link ◽  
European Ancestry ◽  
Association Analyses ◽  
Genome Wide ◽  
Synaptic Neurotransmission ◽  
Impact Accelerometer ◽  
The Uk ◽  
Genetic Contributions

AbstractSleep is an essential homeostatically-regulated state of decreased activity and alertness conserved across animal species, and both short and long sleep duration associate with chronic disease and all-cause mortality1,2. Defining genetic contributions to sleep duration could point to regulatory mechanisms and clarify causal disease relationships. Through genome-wide association analyses in 446,118 participants of European ancestry from the UK Biobank, we discover 78 loci for self-reported sleep duration that further impact accelerometer-derived measures of sleep duration, daytime inactivity duration, sleep efficiency and number of sleep bouts in a subgroup (n=85,499) with up to 7-day accelerometry. Associations are enriched for genes expressed in several brain regions, and for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission, catecholamine production, synaptic plasticity, and unsaturated fatty acid metabolism. Genetic correlation analysis indicates shared biological links between sleep duration and psychiatric, cognitive, anthropometric and metabolic traits and Mendelian randomization highlights a causal link of longer sleep with schizophrenia.

scholarly journals The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anders Martin Fjell ◽  
Hakon Grydeland ◽  
Yunpeng Wang ◽  
Inge K Amlien ◽  
David Bartres-Faz ◽  
...  
Keyword(s):  
Genetic Correlations ◽  
Brain Structures ◽  
Brain Regions ◽  
Nucleotide Polymorphisms ◽  
Coordinated Development ◽  
Volumetric Change ◽  
Cross Sectional ◽  
Genetic Organization ◽  
Development And Aging ◽  
Subcortical Regions

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single nucleotide polymorphisms-based analyses of 38127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

scholarly journals Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Rona J. Strawbridge ◽  
Joey Ward ◽  
Breda Cullen ◽  
Elizabeth M. Tunbridge ◽  
Sarah Hartz ◽  
...  
Keyword(s):  
Risk Taking ◽  
Genetic Correlations ◽  
Uk Biobank ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
The Uk

scholarly journals The transferability of lipid loci across African, Asian and European cohorts

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Karoline Kuchenbaecker ◽  
◽  
Nikita Telkar ◽  
Theresa Reiker ◽  
Robin G. Walters ◽  
...  
Keyword(s):  
Association Studies ◽  
Genetic Risk Score ◽  
Genetic Correlations ◽  
Serum Levels ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genetic Determinants ◽  
Gene Environment ◽  
Genome Wide ◽  
The Uk

Abstract Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r = 0.23–0.28, p < 1.9 × 10−14). Overall, there is evidence of reproducibility for ~75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions.

GENOME-WIDE ANALYSIS OF RISK-TAKING BEHAVIOUR IN 116 255 INDIVIDUALS FROM THE UK BIOBANK COHORT AND CROSS-DISORDER GENETIC CORRELATIONS

2019 ◽  
Vol 29 ◽  
pp. S981-S982
Author(s):  
Rona Strawbridge ◽  
Joey Ward ◽  
Breda Cullen ◽  
Elizabeth Tunbridge ◽  
Sarah Hartz ◽  
...  
Keyword(s):  
Risk Taking ◽  
Genetic Correlations ◽  
Uk Biobank ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
The Uk

scholarly journals Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

2015 ◽  
Vol 77 (8) ◽  
pp. 749-763 ◽  
Author(s):  
Stéphanie Debette ◽  
Carla A. Ibrahim Verbaas ◽  
Jan Bressler ◽  
Maaike Schuur ◽  
Albert Smith ◽  
...  
Keyword(s):  
Older People ◽  
Declarative Memory ◽  
Aging Research ◽  
Genomic Epidemiology ◽  
Genome Wide

scholarly journals Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angli Xue ◽  
Longda Jiang ◽  
Zhihong Zhu ◽  
Naomi R. Wray ◽  
Peter M. Visscher ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Longitudinal Changes ◽  
Genome Wide ◽  
The Uk ◽  
Almost All ◽  
Cardiovascular Traits

AbstractGenome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank (n = 455,607) are more likely to misreport or reduce their alcohol consumption levels, and propose a correction procedure to mitigate the MLC-induced biases. The alcohol consumption GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between alcohol consumption and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of alcohol consumption on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data.

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