scholarly journals Exploring Phenotypic and Genetic Overlap Between Cannabis Use and Schizotypy

2020 ◽  
Vol 23 (4) ◽  
pp. 221-227 ◽  
Author(s):  
James Vaissiere ◽  
Jackson G. Thorp ◽  
Jue-Sheng Ong ◽  
Alfredo Ortega-Alonso ◽  
Eske M. Derks
Keyword(s):  
Multiple Testing ◽  
Association Studies ◽  
Genetic Correlations ◽  
Cannabis Use ◽  
Exact Nature ◽  
Social Anhedonia ◽  
Multiple Testing Correction ◽  
Phenotypic Correlations ◽  
Genetic Overlap ◽  
Heritability Estimates

AbstractThere is a well-established relationship between cannabis use and psychosis, although the exact nature of this relationship is not fully understood. Recent studies have observed significant genetic overlap between a diagnosis of schizophrenia and lifetime cannabis use. Expanding on this work, the current study aimed to examine whether genetic overlap also occurs for subclinical psychosis (schizotypy) and cannabis use, as well as examining the phenotypic association between the traits. Phenotypic correlations were calculated for a variety of schizotypy and cannabis phenotypes in the UK Biobank (UKB), and single nucleotide polymorphism (SNP)-based heritability estimates and genetic correlations were calculated for these UKB phenotypes as well as for several other variables taken from recent genomewide association studies. Positive phenotypic correlations were observed between 11 out of 12 pairs of the cannabis use and schizotypy phenotypes (correlation range .05–.18), indicating a robust association between increased symptoms of schizotypy and cannabis use. SNP-based heritability estimates for two schizotypy phenotypes remained significant after multiple testing correction: social anhedonia (h2SNP = .08, SE = .02, N = 4025) and ever seen an unreal vision (h2SNP = .35, SE = .10, N = 150,717). Finally, one significant genetic correlation was observed between schizotypy and cannabis use, a negative correlation between social anhedonia and number of times used cannabis (rg = −.30, p = .012). The current study suggests the relationship between cannabis use and psychosis is also seen in subclinical symptoms of psychosis, but further research with larger samples is needed to determine the biological mechanisms underlying this association.

scholarly journals Shared Genomic Architectures of Covid-19 and Antisocial Behavior: Implications During Pandemics

2021 ◽  
Author(s):  
Charleen D. Adams ◽  
Jorim Tielbeek ◽  
Brian Boutwell
Keyword(s):  
Computer Games ◽  
Multiple Testing ◽  
Association Studies ◽  
Genetic Correlations ◽  
Gastrointestinal Diseases ◽  
Risk Tolerance ◽  
Chronic Obstructive ◽  
Genome Wide Association Studies ◽  
Multiple Testing Correction ◽  
Obstructive Pulmonary Disease

BACKGROUND. Norm violation, aggression, and antisocial behaviors (ASB) are harmful to society. In times of crisis, such as the current pandemic, individuals with higher antisocial tendencies may subvert efforts to ameliorate social problems. Complicating research on this topic, however, is the fact that variance in both ASB and health traits is partly heritable, suggesting the possibility of genetic correlations between them. METHODS. We characterized the shared polygenic architecture of ASB, Covid-19, and related traits, leveraging summary statistics from genome-wide association studies. RESULTS. After multiple-testing correction, ASB was genetically correlated with average income (rg=-0.54; 95% confidence interval [CI]: -0.65, -0.43); education years (rg=-0.48; CI: -0.59, -0.38; verbal reasoning (rg=-0.44; CI: -0.58, -0.30); healthspan (rg=-0.47; CI: -0.62, -0.31), lifespan (rg=-0.33 (CI: -0.46, -0.21); breastfed as baby (rg=-0.24; 95% CI: -0.38, -0.11); cheese intake (rg=-0.28 (CI: -0.38, -0.18); Covid-19 (rg=0.51, 95% CI: 0.12, 0.90; heavy, manual labor (rg=0.58; CI: 0.45, 0.70); noisy workplace (rg=0.63; CI: 0.48, 0.77); Townsend Deprivation Index (rg=0.70; CI: 0.56, 0.84); gastrointestinal diseases (rg=0.46; 95% CI: 0.23, 0.70); chronic obstructive pulmonary disease (rg=0.51; CI: 0.33, 0.68); genitourinary diseases (rg=0.38; CI: 0.22, 0.55); neuroticism (rg=0.29; CI: 0.20, 0.38); seen doctor for nerves, anxiety, tension, or depression (rg=0.42; CI: 0.31, 0.54); plays computer games (rg=0.15; CI: 0.06, 0.25); violent-crime victim (rg=0.36; CI: 0.16, 0.56); risk tolerance (rg=0.50; CI: 0.39, 0.65); saw sudden violent death (rg=0.42; CI: 0.20, 0.64). CONCLUSIONS. Our results suggest ASB shares genetic architecture with Covid-19 and related health outcomes. We discuss the public-health and bioethical implications of our results.

scholarly journals Realized Sampling Variances of Estimates of Genetic Parameters and the Difference Between Genetic and Phenotypic Correlations

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1409-1416 ◽  
Author(s):  
Kenneth R Koots ◽  
John P Gibson
Keyword(s):  
Genetic Correlation ◽  
Genetic Parameters ◽  
Genetic Parameter ◽  
Genetic Correlations ◽  
Phenotypic Correlation ◽  
Parameter Estimates ◽  
Sampling Variance ◽  
Phenotypic Correlations ◽  
Genetic And Phenotypic Correlations ◽  
Heritability Estimates

Abstract A data set of 1572 heritability estimates and 1015 pairs of genetic and phenotypic correlation estimates, constructed from a survey of published beef cattle genetic parameter estimates, provided a rare opportunity to study realized sampling variances of genetic parameter estimates. The distribution of both heritability estimates and genetic correlation estimates, when plotted against estimated accuracy, was consistent with random error variance being some three times the sampling variance predicted from standard formulae. This result was consistent with the observation that the variance of estimates of heritabilities and genetic correlations between populations were about four times the predicted sampling variance, suggesting few real differences in genetic parameters between populations. Except where there was a strong biological or statistical expectation of a difference, there was little evidence for differences between genetic and phenotypic correlations for most trait combinations or for differences in genetic correlations between populations. These results suggest that, even for controlled populations, estimating genetic parameters specific to a given population is less useful than commonly believed. A serendipitous discovery was that, in the standard formula for theoretical standard error of a genetic correlation estimate, the heritabilities refer to the estimated values and not, as seems generally assumed, the true population values.

scholarly journals 2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sangyoon Yi ◽  
Xianyang Zhang ◽  
Lu Yang ◽  
Jinyan Huang ◽  
Yuanhang Liu ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Statistical Power ◽  
Association Studies ◽  
Control Procedure ◽  
Multiple Testing Correction ◽  
New Approach ◽  
False Discovery ◽  
Traditional Procedure ◽  
Extensive Evaluation ◽  
Confounder Adjustment

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

scholarly journals Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

2018 ◽  
Author(s):  
David M. Howard ◽  
Mark J. Adams ◽  
Toni-Kim Clarke ◽  
Jonathan D. Hafferty ◽  
Jude Gibson ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Drug Repositioning ◽  
Association Studies ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Brain Regions ◽  
Genome Wide Association Studies ◽  
Multiple Testing Correction ◽  
Synaptic Structure ◽  
Genome Wide

AbstractMajor depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.

Genetic parameter estimates (full sib and half sib analysis) of fertility and hatchability in two strains of Rhode Island chickens

2021 ◽  
Vol 38 (1) ◽  
pp. 14-22
Author(s):  
M. Orunmuyi ◽  
I. A. Adeyinka ◽  
O.O Oni
Keyword(s):  
Rhode Island ◽  
Additive Genetic Variance ◽  
Genetic Parameter ◽  
Genetic Correlations ◽  
Reproductive Traits ◽  
Parameter Estimates ◽  
Phenotypic Correlations ◽  
Poultry Breeding ◽  
Genetic And Phenotypic Correlations ◽  
Heritability Estimates

A study was conducted to estimate the genetic parameters of fertility and hatchability in two strains of Rhode Island Red (RIR) Chickens denoted as Strain A and Strain B respectively using the full-sib (sire +dam variance) and maternal half-sib (dam variance) components. The birds were obtained from the selected populations of RIR Chickens kept at the poultry breeding programme of National Animal Production Research Institute, Shika, Zaria, Nigeria. Settable eggs were collected from mating 28 cocks to 252 hens in a ratio of 1cock:9 hens from each strain. Eggs were pedigreed according to sire and dam. Results showed that values obtained for number of egg set (EGGSET), number of fertile eggs (NFERT), number of hatched chicks (NHATCH), percentage of chicks hatched from total eggs set (PHATCH) and percentage of chicks hatched from fertile eggs (PHATCHBL) were all higher in strain A than strain B. Heritability estimates obtained from the full-sib and maternal half-sib analysis ranged from medium to high for the two strains (0.24-0.96). The maternal half sib estimates were higher (0.40-0.96) than the estimates obtained from full sibs (0.24- 0.48). Genetic and phenotypic correlations obtained for both strains were positive and similar regardless of method of estimation. Genetic correlations between EGGSET and PFERT were low in strain A using both full-sib and maternal half-sib analyses (0.09-0.14). Phenotypic correlations between EGGSET and PFERT, PHATCH and PHATCHBL were also low in both strains and regardless of method of analyses. Moderate to high heritability estimates suggest that genetic improvement can be obtained by selection of these reproductive traits. The full-sib analysis for estimating heritability will be preferred since it is assumed that only additive genetic variance contributes to the covariance between family members.

Estimates of genetic and phenotypic parameters of some weight and fleece traits in a coarse-wool breed of sheep

1982 ◽  
Vol 99 (2) ◽  
pp. 277-285 ◽  
Author(s):  
R. A. Guirgis ◽  
E. A. Afifi ◽  
E. S. E. Galal
Keyword(s):  
Body Weight ◽  
Genetic Correlations ◽  
Phenotypic Correlations ◽  
Body Weights ◽  
Heritability Estimates ◽  
Fleece Weight ◽  
Staple Length

SUMMARYA study using 1150 lambs to estimate genetic and phenotypic parameters of some weight and fleece traits was carried out on coarse-wool Barki sheep. The weight traits were birth, weaning, yearling weights and daily gains whereas fleece traits included kemp score, staple length and greasy-fleece weight.Heritability estimates of weight traits were within the range 0·25–0·30. Those of fleece traits were 0·16, 0·21 and 0·43. The repeatability estimates of fleece traits were 0·18, 0·38 and 0·53 for staple length, greasy-fleece weight and kemp score respectively.Phenotypic correlations between body weight and fleece traits were mostly positive. Genetic correlations between greasy-fleece weight and body weights were mostly positive and of medium values. Those between kemp score and body weights were mostly negative, ranging from medium-high to high.

RELATIONSHIPS OF REPRODUCTION TRAITS, BODY WEIGHT AND MILK YIELD IN DAIRY CATTLE

1986 ◽  
Vol 66 (1) ◽  
pp. 53-65 ◽  
Author(s):  
T. R. BATRA ◽  
A. J. LEE ◽  
A. J. McALLISTER
Keyword(s):  
Body Weight ◽  
Dairy Cattle ◽  
Milk Yield ◽  
Fixed Effects ◽  
Genetic Correlations ◽  
Calving Interval ◽  
Phenotypic Correlations ◽  
Reproduction Traits ◽  
Heritability Estimates ◽  
National Cooperative

The relationships between reproduction traits, body weight and milk yield were investigated using data from 1611 heifers and 733 cows from two lines of the National Cooperative Dairy Cattle Breeding Project. The data were analyzed separately for heifers and cows within lines using a mixed linear model containing fixed effects for station, year of birth, season of birth and random effect of sires. Heritability estimates and genetic correlations were estimated by a paternal half-sib analysis. Heritability estimates for heifer and cow reproduction traits ranged between 0 and 26% while those of body weights at calving and 112 d postpartum and milk yield ranged from 24 to 43%. Heifers with difficult calving had a higher incidence of retained placenta than those with normal calving. Phenotypic correlations between heifer reproduction traits and milk yield during first lactation were small. High milk production in cows was associated with longer calving interval. Phenotypic correlations between heifer's and cow's reproduction traits were small. Difficult calving in heifers impairs reproductive performance after calving resulting in greater number of days from calving to first and last breeding and leading to a longer calving interval. Key words: Reproduction traits, heifers, cows, milk yield, dairy cattle

Optimum selection age for wood density in loblolly pine

2002 ◽  
Vol 32 (8) ◽  
pp. 1393-1399 ◽  
Author(s):  
D P Gwaze ◽  
K J Harding ◽  
R C Purnell ◽  
F E Bridgwater
Keyword(s):  
Linear Relationship ◽  
Wood Density ◽  
Genetic Correlations ◽  
Core Density ◽  
Individual Tree ◽  
Phenotypic Correlations ◽  
Age Related ◽  
Optimum Selection ◽  
Heritability Estimates ◽  
Optimum Selection Age

Genetic and phenotypic parameters for core wood density of Pinus taeda L. were estimated for ages ranging from 5 to 25 years at two sites in southern United States. Heritability estimates on an individual-tree basis for core density were lower than expected (0.20–0.31). Age–age genetic correlations were higher than phenotypic correlations, particularly those involving young ages. Age–age genetic correlations were high, being greater than 0.75. Age–age genetic correlations had a moderately linear relationship, while age–age phenotypic correlations had a strong linear relationship with natural logarithm of age ratio. Optimum selection age for core density was estimated to be 5 years when calculations were based on both genetic and phenotypic correlations. However, age 5 was the youngest examined in this study and optimum selection age may be younger than 5. Generally, the optimum selection age was robust to changes in breeding phase and assumptions concerning age-related variation in heritability estimates. Early selection for core density would result in a correlated increase in earlywood density but little progress in latewood density or latewood proportion at maturity.

scholarly journals Sleep Deficits and Cannabis Use Behaviors: An Analysis of Shared Genetics Using Linkage Disequilibrium Score Regression and Polygenic Risk Prediction

2020 ◽  
Author(s):  
Evan A. Winiger ◽  
Jarrod M. Ellingson ◽  
Claire L. Morrison ◽  
Robin P. Corley ◽  
Joëlle A. Pasman ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Sleep Duration ◽  
Association Studies ◽  
Genetic Correlations ◽  
Cannabis Use ◽  
European Ancestry ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Short Sleep Duration ◽  
Polygenic Risk

AbstractStudy ObjectivesEstimate the genetic relationship of cannabis use with sleep deficits and eveningness chronotype.MethodsWe used linkage disequilibrium score regression (LDSC) to analyze genetic correlations between sleep deficits and cannabis use behaviors. Secondly, we generated sleep deficit polygenic risk scores (PRSs) and estimated their ability to predict cannabis use behaviors using logistic regression. Summary statistics came from existing genome wide association studies (GWASs) of European ancestry that were focused on sleep duration, insomnia, chronotype, lifetime cannabis use, and cannabis use disorder (CUD). A target sample for PRS prediction consisted of high-risk participants and participants from twin/family community-based studies (n = 796, male = 66%; mean age = 26.81). Target data consisted of self-reported sleep (sleep duration, feeling tired, and taking naps) and cannabis use behaviors (lifetime use, number of lifetime uses, past 180-day use, age of first use, and lifetime CUD symptoms).ResultsSignificant genetic correlation between lifetime cannabis use and eveningness chronotype (rG = 0.24, p < 0.01), as well as between CUD and both short sleep duration (<7 h) (rG = 0.23, p = 0.02) and insomnia (rG = 0.20, p = 0.02). Insomnia PRS predicted earlier age of first cannabis use (β = −0.09, p = 0.02) and increased lifetime CUD symptom count use (β = 0.07, p = 0.03).ConclusionCannabis use is genetically associated with both sleep deficits and an eveningness chronotype, suggesting that there are genes that predispose individuals to both cannabis use and sleep deficits.

scholarly journals False discovery rates for genome-wide association tests in biobanks with thousands of phenotypes

2021 ◽  
Author(s):  
Aubrey Annis ◽  
Anita Pandit ◽  
Jonathon LeFaive ◽  
Sarah Gagliano Taliun ◽  
Lars Fritsche ◽  
...  
Keyword(s):  
Genetic Association ◽  
Multiple Testing ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Minor Allele ◽  
Type I ◽  
Allele Carrier ◽  
Multiple Testing Correction ◽  
Phenotypic Data ◽  
False Discovery

Abstract Biobanks housing genetic and phenotypic data for thousands of individuals introduce new opportunities and challenges for genetic association studies. Association testing across many phenotypes increases the multiple-testing burden and correlation between phenotypes makes appropriate multiple-testing correction uncertain. Moreover, analysis including low-frequency variants results in inflated type I error due to the much larger number of tests and the elevated importance of each individual minor allele carrier in those tests. Here we demonstrate that standard Bonferroni and permutation-based methods for multiple testing correction are inadequate for a holistic analysis of biobank data because ideal significance thresholds vary across datasets and minor allele frequencies. We propose a single-iteration permutation method that is computationally feasible and provides false discovery rate (FDR) estimates tailored to individual datasets and variant frequencies. Each dataset’s unique FDR estimates provide customized levels of confidence for association results and enable informed interpretation of genetic association studies across the phenome.

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