scholarly journals Shared components of heritability across genetically correlated traits

2021 ◽  
Author(s):  
Jenna Lee Ballard ◽  
Luke Jen O'Connor
Keyword(s):  
Genetic Variants ◽  
Statistical Power ◽  
Simulated Data ◽  
Effect Sizes ◽  
Correlated Traits ◽  
Posterior Mean ◽  
Out Of Sample ◽  
Shared Component ◽  
Highly Correlated ◽  
The Relationship

Most disease-associated genetic variants are pleiotropic, affecting multiple genetically correlated traits. Their pleiotropic associations can be mechanistically informative: if many variants have similar patterns of association, they may act via similar pleiotropic mechanisms, forming a shared component of heritability. We developed Pleiotropic Decomposition Regression (PDR) to identify shared components and their underlying genetic variants. We validated PDR on simulated data and identified limitations of existing methods in recovering the true components. We applied PDR to three clusters of 5-6 traits genetically correlated with coronary disease, asthma, and type II diabetes respectively, producing biologically interpretable components. For CAD, PDR identified components related to BMI, hypertension and cholesterol, and it clarified the relationship among these highly correlated risk factors. We assigned variants to components, calculated their posterior-mean effect sizes, and performed out-of-sample validation. Our posterior-mean effect sizes pool statistical power across traits and substantially boost the correlation (r2) between true and estimated effect sizes compared with the original summary statistics: by 94% and 70% for asthma and T2D out of sample, and by a predicted 300% for CAD.

scholarly journals The Relationship between Family Violence and Self-Control in Adolescence: A Multi-Level Meta-Analysis

2018 ◽  
Vol 15 (11) ◽  
pp. 2468 ◽  
Author(s):  
Yayouk Willems ◽  
Jian-Bin Li ◽  
Anne Hendriks ◽  
Meike Bartels ◽  
Catrin Finkenauer
Keyword(s):  
Family Violence ◽  
Statistical Power ◽  
Meta Analysis ◽  
Time Lag ◽  
Self Control ◽  
Effect Sizes ◽  
Future Research ◽  
Multi Level ◽  
Low Self Control ◽  
The Relationship

Theoretical studies propose an association between family violence and low self-control in adolescence; however, empirical findings of this association are inconclusive. The aim of the present research was to systematically summarize available findings on the relation between family violence and self-control across adolescence. We included 28 studies with 143 effect sizes, representing more than 25,000 participants of eight countries from early to late adolescence. Applying a three-level meta-analysis, taking dependency between effect sizes into account while retaining statistical power, we examined the magnitude and direction of the overall effect size. Additionally, we investigated whether theoretical moderators (e.g., age, gender, country), and methodological moderators (e.g., time lag between family violence and self-control, informant) influenced the magnitude of the association between family violence and self-control. Our results revealed that family violence and self-control have a small to moderate significant negative association (r = −0.191). This association did not vary across gender, country, and informants. The strength of the association, however, decreased with age and in longitudinal studies. This finding provides evidence that researchers and clinicians may expect low self-control in the wake of family violence, especially in early adolescence. Recommendations for future research in the area are discussed.

scholarly journals Promoter sequence and architecture determine expression variability and confer robustness to genetic variants

2021 ◽  
Author(s):  
Hjorleifur Einarsson ◽  
Marco Salvatore ◽  
Christian Vaagenso ◽  
Nicolas Alcaraz ◽  
Jette Bornholdt Lange ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Binding Sites ◽  
Promoter Sequence ◽  
Effect Sizes ◽  
Regulatory Mechanisms ◽  
Transcription Start ◽  
Mutational Robustness ◽  
Expression Variability ◽  
Transcription Start Sites ◽  
The Relationship

Genetic and environmental exposures cause variability in gene expression. Although most genes are affected in a population, their effect sizes vary greatly, indicating the existence of regulatory mechanisms that could amplify or attenuate expression variability. Here, we investigate the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals. We find that expression variability is largely determined by a promoter's DNA sequence and its binding sites for specific transcription factors. We further demonstrate that flexible usage of transcription start sites within a promoter attenuates variability, providing transcriptional and mutational robustness.

The Limits of Ego Depletion

2019 ◽  
Vol 50 (5-6) ◽  
pp. 292-304 ◽  
Author(s):  
Mario Wenzel ◽  
Marina Lind ◽  
Zarah Rowland ◽  
Daniela Zahn ◽  
Thomas Kubiak
Keyword(s):  
Research Agenda ◽  
Statistical Power ◽  
Interindividual Variability ◽  
Ego Depletion ◽  
Crossover Design ◽  
Effect Sizes ◽  
Future Research ◽  
Future Research Agenda ◽  
Depletion Effect ◽  
Within Subjects

Abstract. Evidence on the existence of the ego depletion phenomena as well as the size of the effects and potential moderators and mediators are ambiguous. Building on a crossover design that enables superior statistical power within a single study, we investigated the robustness of the ego depletion effect between and within subjects and moderating and mediating influences of the ego depletion manipulation checks. Our results, based on a sample of 187 participants, demonstrated that (a) the between- and within-subject ego depletion effects only had negligible effect sizes and that there was (b) large interindividual variability that (c) could not be explained by differences in ego depletion manipulation checks. We discuss the implications of these results and outline a future research agenda.

Do Extra-Platelet Sources Contribute to the Plasma Level of Thrombospondin?

1988 ◽  
Vol 59 (02) ◽  
pp. 273-276 ◽  
Author(s):  
J Dawes ◽  
D A Pratt ◽  
M S Dewar ◽  
F E Preston
Keyword(s):  
Platelet Count ◽  
Background Concentration ◽  
Serum Concentrations ◽  
Bone Marrow Depression ◽  
Serial Sampling ◽  
Control Serum ◽  
Platelet Release ◽  
Highly Correlated ◽  
The Relationship

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

Migraine: Genetic Variants and Clinical Phenotypes

2019 ◽  
Vol 26 (34) ◽  
pp. 6207-6221 ◽  
Author(s):  
Innocenzo Rainero ◽  
Alessandro Vacca ◽  
Flora Govone ◽  
Annalisa Gai ◽  
Lorenzo Pinessi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Mthfr Gene ◽  
Genome Wide Association Studies ◽  
Clinical Phenotypes ◽  
Network Analyses ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Common ◽  
The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

Multifinality, equifinality, and fanning: Developmental concepts and statistical implications

2021 ◽  
pp. 016502542110204
Author(s):  
Ben Hinnant ◽  
John Schulenberg ◽  
Justin Jager
Keyword(s):  
Interindividual Variability ◽  
Growth Models ◽  
Practical Importance ◽  
Simulated Data ◽  
Developmental Changes ◽  
Effect Sizes ◽  
Over Time ◽  
Developmental Window

Multifinality, equifinality, and fanning are important developmental concepts that emphasize understanding interindividual variability in trajectories over time. However, each concept implies that there are points in a developmental window where interindividual variability is more limited. We illustrate the multifinality concept under manipulations of variance in starting points, using both normal and zero-inflated simulated data. Results indicate that standardized estimates and effect sizes are inflated when predicting components of growth models with limited interindividual variance, which could lead to overinterpretation of the practical importance of findings. Conceptual implications are considered and recommendations are provided for evaluating developmental changes in common situations that researchers may encounter.

scholarly journals Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

2021 ◽  
Author(s):  
Andrew A. Crawford ◽  
◽  
Sean Bankier ◽  
Elisabeth Altmaier ◽  
Catriona L. K. Barnes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Genetic Variants ◽  
Plasma Cortisol ◽  
Statistical Power ◽  
Mendelian Randomisation ◽  
Eqtl Analysis ◽  
Causative Role ◽  
Peripheral Tissues ◽  
Corticosteroid Binding Globulin

AbstractThe stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06–0.59) and myocardial infarction (0.21, 95% CI 0.00–0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

THE RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNOEA AND TASK-1 GENETIC VARIANTS

2018 ◽  
Vol 36 (Supplement 1) ◽  
pp. e205
Author(s):  
N. Li ◽  
T. Shi ◽  
X. Yao ◽  
Y. Wang ◽  
M. Heizhati ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Genetic Variants ◽  
Sleep Apnoea ◽  
Obstructive Sleep ◽  
The Relationship ◽  
And Task

Prediction of Hearing Threshold in Infants Using Auditory Steady-State Evoked Potentials

2002 ◽  
Vol 13 (05) ◽  
pp. 236-245 ◽  
Author(s):  
Gary Rance ◽  
Field Rickards
Keyword(s):  
Hearing Loss ◽  
Steady State ◽  
Hearing Threshold ◽  
Normal Hearing ◽  
Older Children ◽  
Behavioral Thresholds ◽  
Similar Threshold ◽  
Highly Correlated ◽  
The Relationship ◽  
Audiometric Test

This retrospective study examines the relationship between auditory steady-state evoked potential (ASSEP) thresholds determined in infancy and subsequently obtained behavioral hearing levels in children with normal hearing or varying degrees of sensorineural hearing loss. Overall, the results from 211 subjects showed that the two test techniques were highly correlated, with Pearson r values exceeding .95 at each of the audiometric test frequencies between 500 and 4000 Hz. Analysis of the findings for babies with significant hearing loss (moderate to profound levels) showed similar threshold relationships to those obtained in previous studies involving adults and older children. The results for infants with normal or near-normal hearing did, however, differ from those reported for older subjects, with behavioral thresholds typically 10 to 15 dB better than would have been predicted from their ASSEP levels.

scholarly journals Recipient and donor genetic variants associated with mortality after allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 4 (14) ◽  
pp. 3224-3233
Author(s):  
Paul J. Martin ◽  
David M. Levine ◽  
Barry E. Storer ◽  
Sarah C. Nelson ◽  
Xinyuan Dong ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Genetic Variants ◽  
Hematopoietic Cell Transplantation ◽  
Genome Wide Association Study ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
European Ancestry ◽  
A Genome ◽  
Grade 3 ◽  
Highly Correlated

Abstract Many studies have suggested that genetic variants in donors and recipients are associated with survival-related outcomes after allogeneic hematopoietic cell transplantation (HCT), but these results have not been confirmed. Therefore, the utility of testing genetic variants in donors and recipients for risk stratification or understanding mechanisms leading to mortality after HCT has not been established. We tested 122 recipient and donor candidate variants for association with nonrelapse mortality (NRM) and relapse mortality (RM) in a cohort of 2560 HCT recipients of European ancestry with related or unrelated donors. Associations discovered in this cohort were tested for replication in a separate cohort of 1710 HCT recipients. We found that the donor rs1051792 A allele in MICA was associated with a lower risk of NRM. Donor and recipient rs1051792 genotypes were highly correlated, making it statistically impossible to determine whether the donor or recipient genotype accounted for the association. Risks of grade 3 to 4 graft-versus-host disease (GVHD) and NRM in patients with grades 3 to 4 GVHD were lower with donor MICA-129Met but not with MICA-129Val, implicating MICA-129Met in the donor as an explanation for the decreased risk of NRM after HCT. Our analysis of candidate variants did not show any other association with NRM or RM. A genome-wide association study did not identify any other variants associated with NRM or RM.

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