scholarly journals A novel framework for analysis of the shared genetic background of correlated traits

2021 ◽  
Author(s):  
Gulnara R. Svishcheva ◽  
Evgeny S. Tiys ◽  
Elizaveta E. Elgaeva ◽  
Sofia G. Feoktistova ◽  
Paul R. H. J. Timmers ◽  
...  
Keyword(s):  
Genetic Background ◽  
Genetic Variance ◽  
Genetic Factors ◽  
Summary Statistics ◽  
Simulation Studies ◽  
Correlated Traits ◽  
Genetic And Phenotypic Correlations ◽  
Psychiatric Conditions ◽  
Variance Explained ◽  
Shared Genetic

We propose a novel effective framework for analysis of the shared genetic background for a set of genetically correlated traits using SNP-level GWAS summary statistics. This framework called SHAHER is based on the construction of a linear combination of traits by maximizing the proportion of its genetic variance explained by the shared genetic factors. SHAHER requires only full GWAS summary statistics and matrices of genetic and phenotypic correlations between traits as inputs. Our framework allows both shared and unshared genetic factors to be to effectively analyzed. We tested our framework using simulation studies, compared it with previous developments, and assessed its performance using three real datasets: anthropometric traits, psychiatric conditions and lipid concentrations. SHAHER is versatile and applicable to summary statistics from GWASs with arbitrary sample sizes and sample overlaps, allows incorporation of different GWAS models (Cox, linear and logistic) and is computationally fast.

Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis

2021 ◽  
Vol 23 ◽  
Author(s):  
Pei He ◽  
Rong- Rong Cao ◽  
Fei- Yan Deng ◽  
Shu- Feng Lei
Keyword(s):  
Association Study ◽  
Canonical Correlation ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Summary Statistics ◽  
Immune Disease ◽  
Histocompatibility Complex ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Shared Genetic

Background: Immune and skeletal systems physiologically and pathologically interact with each other. The immune and skeletal diseases may share potential pleiotropic genetics factors, but the shared specific genes are largely unknown Objective: This study aimed to investigate the overlapping genetic factors between multiple diseases (including rheumatoid arthritis (RA), psoriasis, osteoporosis, osteoarthritis, sarcopenia and fracture) Methods: The canonical correlation analysis (metaCCA) approach was used to identify the shared genes for six diseases by integrating genome-wide association study (GWAS)-derived summary statistics. Versatile Gene-based Association Study (VEGAS2) method was further applied to refine and validate the putative pleiotropic genes identified by metaCCA. Results: About 157 (p<8.19E-6), 319 (p<3.90E-6) and 77 (p<9.72E-6) potential pleiotropic genes were identified shared by two immune disease, four skeletal diseases, and all of the six diseases, respectively. The top three significant putative pleiotropic genes shared by both immune and skeletal diseases, including HLA-B, TSBP1 and TSBP1-AS1 (p<E-300) were located in the major histocompatibility complex (MHC) region. Nineteen of 77 putative pleiotropic genes identified by metaCCA analysis were associated with at least one disease in the VEGAS2 analysis. Specifically, majority (18) of these 19 putative validated pleiotropic genes were associated with RA. Conclusion: The metaCCA method identified some pleiotropic genes shared by the immune and skeletal diseases. These findings help to improve our understanding of the shared genetic mechanisms and signaling pathways underlying immune and skeletal diseases.

scholarly journals Stratifying depression by neuroticism: revisiting a diagnostic tradition using GWAS data

2019 ◽  
Author(s):  
Mark J. Adams ◽  
David M. Howard ◽  
Michelle Luciano ◽  
Toni-Kim Clarke ◽  
Gail Davies ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Genetic Variance ◽  
Genetic Factors ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Major Depressive ◽  
Genome Wide ◽  
Genetic Contributions

AbstractMajor depressive disorder and neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. We analysed two sets of summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium and 23andMe) and compared them to GWAS of neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with neuroticism. We found evidence that most genetic variants associated with depression are likely to be shared with neuroticism. The overlapping common genetic variance of depression and neuroticism was negatively genetically correlated with cognitive function and positively genetically correlated with several psychiatric disorders. We found that the genetic contributions unique to depression, and not shared with neuroticism, were correlated with inflammation, cardiovascular disease, and sleep patterns. Our findings demonstrate that, while genetic risk factors for depression are largely shared with neuroticism, there are also non-neuroticism related features of depression that may be useful for further patient or phenotypic stratification.

scholarly journals Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

2020 ◽  
Author(s):  
Josine L Min ◽  
Gibran Hemani ◽  
Eilis Hannon ◽  
Koen F Dekkers ◽  
Juan Castillo-Fernandez ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Variants ◽  
Complex Traits ◽  
Genetic Architecture ◽  
Genetic Variance ◽  
Genetic Factors ◽  
Additive Genetic Variance ◽  
Genetic Influences ◽  
Methylation Quantitative Trait Loci ◽  
Shared Genetic

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.

scholarly journals A Common Genetic Influence on Human Intensity Ratings of Sugars and High-Potency Sweeteners

2015 ◽  
Vol 18 (4) ◽  
pp. 361-367 ◽  
Author(s):  
Liang-Dar Hwang ◽  
Gu Zhu ◽  
Paul A. S. Breslin ◽  
Danielle R. Reed ◽  
Nicholas G. Martin ◽  
...  
Keyword(s):  
Genetic Variance ◽  
Genetic Factors ◽  
Multivariate Modeling ◽  
High Potency ◽  
Sweetness Intensity ◽  
History Of ◽  
Adolescent And Young Adults ◽  
Single Set ◽  
Common Genetic Factor ◽  
Shared Genetic

The perception of sweetness varies among individuals but the sources of this variation are not fully understood. Here, in a sample of 1,901 adolescent and young adults (53.8% female; 243 MZ and 452 DZ twin pairs, 511 unpaired individuals; mean age 16.2 ± 2.8, range 12–26 years), we studied the variation in the perception of sweetness intensity of two monosaccharides and two high-potency sweeteners: glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame. Perceived intensity for all sweeteners decreased with age (2–5% per year) and increased with the history of otitis media (6–9%). Males rated aspartame slightly stronger than females (7%). We found similar heritabilities for sugars (glucose: h2 = 0.31, fructose: h2 = 0.34) and high-potency sweeteners (NHDC: h2 = 0.31, aspartame: h2 = 0.30); all were in the modest range. Multivariate modeling showed that a common genetic factor accounted for >75% of the genetic variance in the four sweeteners, suggesting that individual differences in perceived sweet intensity, which are partly due to genetic factors, may be attributed to a single set of genes. This study provided evidence of the shared genetic pathways between the perception of sugars and high-potency sweeteners.

scholarly journals Genetic and environmental architecture of conscientiousness in adolescence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Takahashi ◽  
Anqing Zheng ◽  
Shinji Yamagata ◽  
Juko Ando
Keyword(s):  
Individual Differences ◽  
Effortful Control ◽  
Genetic Variance ◽  
Genetic Factors ◽  
Common Factor ◽  
Genetic Correlations ◽  
Self Control ◽  
Genetic Analyses ◽  
Environmental Correlations ◽  
Per Se

AbstractUsing a genetically informative design (about 2000 twin pairs), we investigated the phenotypic and genetic and environmental architecture of a broad construct of conscientiousness (including conscientiousness per se, effortful control, self-control, and grit). These four different measures were substantially correlated; the coefficients ranged from 0.74 (0.72–0.76) to 0.79 (0.76–0.80). Univariate genetic analyses revealed that individual differences in conscientiousness measures were moderately attributable to additive genetic factors, to an extent ranging from 62 (58–65) to 64% (61–67%); we obtained no evidence that shared environmental influences were observed. Multivariate genetic analyses showed that for the four measures used to assess conscientiousness, genetic correlations were stronger than the corresponding non-shared environmental correlations, and that a latent common factor accounted for over 84% of the genetic variance. Our findings suggest that individual differences in the four measures of conscientiousness are not distinguishable at both the phenotypic and behavioural genetic levels, and that the overlap was substantially attributable to genetic factors.

scholarly journals Sapling and coppice biomass heritabilities and potential gains from Eucalyptus polybractea progeny trials

2021 ◽  
Vol 17 (2) ◽  
Author(s):  
Beren Spencer ◽  
Richard Mazanec ◽  
Mark Gibberd ◽  
Ayalsew Zerihun
Keyword(s):  
Western Australia ◽  
Growth Rates ◽  
Genetic Parameters ◽  
Genetic Variance ◽  
Additive Genetic Variance ◽  
Short Rotation ◽  
Sapling Growth ◽  
Genetic And Phenotypic Correlations ◽  
Breeding Selections ◽  
Cross Site

AbstractEucalyptus polybractea has been planted as a short-rotation coppice crop for bioenergy in Western Australia. Historical breeding selections were based on sapling biomass and despite a long history as a coppice crop, the genetic parameters of coppicing are unknown. Here, we assessed sapling biomass at ages 3 and 6 from three progeny trials across southern Australia. After the second sapling assessment, all trees were harvested. Coppice biomass was assessed 3.5 years later. Mortality following harvest was between 1 and 2%. Additive genetic variance for the 6-sapling estimate at one site was not significant. Sapling heritabilities were between 0.06 and 0.36 at 3 years, and 0.18 and 0.20 at 6 years. The heritability for the coppice biomass was between 0.07 and 0.17. Within-site genetic and phenotypic correlations were strong between all biomass assessments. Cross-site correlations were not different from unity. Selections based on net breeding values revealed positive gains in sapling and coppice biomass. Lower or negative gains were estimated if 3-year sapling selections were applied to the coppice assessments (−7.1% to 3.4%) with useful families culled. Positive gains were obtained if 6-year sapling selections were applied to the coppice assessment (6.4% to 9.3%) but these were lower than those obtained by applying coppice selections to the coppice assessment (8.4% to 14.8%). Removal of poor performing families and families that displayed fast sapling growth rates but under-performed as coppice will benefit potential coppice production. These results indicate that selections should be made using coppice data.

Genetic evaluation of production traits between and within flocks of Merino sheep. I. Hogget fleece weights, body weight and wool quality

1989 ◽  
Vol 40 (2) ◽  
pp. 433 ◽  
Author(s):  
SI Mortimer ◽  
KD Atkins
Keyword(s):  
Body Weight ◽  
Environmental Effects ◽  
Genetic Variance ◽  
Research Centre ◽  
Production Traits ◽  
Merino Sheep ◽  
Wool Production ◽  
Phenotypic Correlations ◽  
Genetic And Phenotypic Correlations ◽  
Fleece Weight

Wool production traits were measured on Merino hogget ewes in an unselected multiple-bloodline flock over a 7-year period at Trangie Agricultural Research Centre, N.S.W. The traits measured were greasy fleece weight (GFW), skirted fleece weight (SKFW), yield (Y), clean fleece weight (CFW), fibre diameter (FD), body weight (BWT) and staple length (SL). These measurements were used to examine genetic differences between and within flocks of Merino sheep, and to estimate heritability of and genetic and phenotypic correlations among these traits. Significant strain, flock within strain and flock effects were present for all traits. Interactions between these effects and year were non-significant. Within-flock genetic variance was always larger than between-flock within strain genetic variance for each trait. The influence of environmental effects on these traits was also examined. The environmental effects of birth-rearing type, age at observation and age of dam together accounted for about 7-10% of the total within-flock variation in fleece weights and body weight.After adjusting for significant environmental effects, paternal half-sib heritability estimates were 0.29 �. 0.06 for GFW, 0.22 � 0.05 for SKFW, 0.35 � 0.05 for Y, 0.30 �0.06 for CFW, 0.48 �0.07 for FD, 0.34 �. 0.06 for BWT and 0.44 �0.07 for SL. Estimates for genetic and phenotypic correlations were in agreement with published estimates except for the genetic correlation between CFW and FD (0.40 �. 0.11), and the genetic correlations involving BWT, which were essentially zero. The implications of the results of this study for the genetic improvement of Merino sheep for wool production are discussed.

Association between Polygenic Risk Scores for ADHD and Asthma: A Birth Cohort Investigation

2021 ◽  
pp. 108705472110201
Author(s):  
Douglas Teixeira Leffa ◽  
Bernardo Horta ◽  
Fernando C. Barros ◽  
Ana M. B. Menezes ◽  
Thais Martins-Silva ◽  
...  
Keyword(s):  
Birth Cohort ◽  
Genetic Background ◽  
Adult Adhd ◽  
Risk Scores ◽  
Asthma Diagnosis ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Genetic Overlap ◽  
Genetic Mechanisms ◽  
Shared Genetic

Objective: Shared genetic mechanisms have been hypothesized to explain the comorbidity between ADHD and asthma. To evaluate their genetic overlap, we relied on data from the 1982 Pelotas birth cohort to test the association between polygenic risk scores (PRSs) for ADHD (ADHD-PRSs) and asthma, and PRSs for asthma (asthma-PRSs) and ADHD. Method: We analyzed data collected at birth, 2, 22, and 30 years from 3,574 individuals. Results: Subjects with ADHD had increased risk of having asthma (OR 1.92, 95% CI 1.01–3.66). The association was stronger for females. Our results showed no evidence of association between ADHD-PRSs and asthma or asthma-PRSs and ADHD. However, an exploratory analysis suggested that adult ADHD might be genetically associated with asthma. Conclusion: Our results do not support a shared genetic background between both conditions. Findings should be viewed in light of important limitations, particularly the sample size and the self-reported asthma diagnosis. Studies in larger datasets are required to better explore the genetic overlap between adult ADHD and asthma.

scholarly journals GxEsum: a novel approach to estimate the phenotypic variance explained by genome-wide GxE interaction based on GWAS summary statistics for biobank-scale data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jisu Shin ◽  
Sang Hong Lee
Keyword(s):  
Complex Traits ◽  
Error Rates ◽  
Type I ◽  
Phenotypic Variance ◽  
Environment Interaction ◽  
Summary Statistics ◽  
Gxe Interaction ◽  
Genome Wide ◽  
Scale Data ◽  
Variance Explained

AbstractGenetic variation in response to the environment, that is, genotype-by-environment interaction (GxE), is fundamental in the biology of complex traits and diseases. However, existing methods are computationally demanding and infeasible to handle biobank-scale data. Here, we introduce GxEsum, a method for estimating the phenotypic variance explained by genome-wide GxE based on GWAS summary statistics. Through comprehensive simulations and analysis of UK Biobank with 288,837 individuals, we show that GxEsum can handle a large-scale biobank dataset with controlled type I error rates and unbiased GxE estimates, and its computational efficiency can be hundreds of times higher than existing GxE methods.

Neural Tube Defects: A Two-Pronged Approach to Primary Prevention

PEDIATRICS ◽  
1982 ◽  
Vol 70 (4) ◽  
pp. 648-650
Author(s):  
K. M. Laurence
Keyword(s):  
Folic Acid ◽  
Primary Prevention ◽  
Environmental Factors ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Background ◽  
Genetic Factors ◽  
Maternal Nutrition ◽  
Folic Acid Deficiency ◽  
Acid Deficiency

It is generally agreed that neural tube defects (NTD) have a multifactorial etiology when genetic factors render the developing fetus susceptible to intrauterine environmental factors acting during the fourth week of gestation to interfere with the orderly closure of the neural tube.1 As there is little likelihood that anything can be done about the genetic background, primary prevention would therefore be dependent on eliminating these factors from the environment or avoiding them. My intention here is to enlarge on some aspects of primary prevention of NTD as outlined by Smithells in an earlier issue (Pediatrics 69:498, 1982).2 One environmental factor, poor maternal nutrition and, more particularly, folic acid deficiency seems now to have been identified, but there are almost certainly a number of others.

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