Positive Genetic Correlations Research Articles

Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders.

Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D - IBD) contributing to T2D's relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and bidirectionally with GERD. Gene-based analyses reveal a gene-level genetic overlap between T2D and GI disorders and identify several shared genes reaching genome-wide significance. Pathway-based study implicates leptin (T2D - IBD), thyroid, interferon, and notch signalling (T2D - IBS), abnormal circulating calcium (T2D - PUD), cardiovascular, viral, proinflammatory and (auto)immune-mediated mechanisms in T2D and GI disorders. These findings support a risk-increasing genetic overlap between T2D and GI disorders (except IBD), implicate shared biological pathways with putative causality for certain T2D - GI pairs, and identify targets for further investigation.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Associations between varicose veins and heart failure: A genetic correlation and mendelian randomization study.

Varicose veins and heart failure (HF) are increasingly prevalent. Although numbers of observational studies have indicated that varicose veins might contribute to the risk of HF, the causal relationship between them remains unclear due to the uncontrolled confounding factors and reverse causation bias. Therefore, this study aimed to explore the potential causal relationship between varicose veins and HF. Based on publicly released genome-wide association studies (GWAS), gene correlation was assessed using linkage disequilibrium score (LDSC) regression, and we conducted a two-sample Mendelian randomization (TSMR) analysis to infer the causal relationship. We performed the Inverse variance weighted (IVW) method as the primary analysis, and used Weighted median, MR-Egger, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods to detect and correct for horizontal pleiotropy. LDSC revealed there was a positive genetic correlation between varicose veins and HF (rg = 0.1726184, Se = 0.04511803, P = .0001). The results of the IVW method indicated that genetically predicted varicose veins were associated with an increased risk of HF (odds ratio (OR) = 1.03; 95% confidence interval (CI): 1.01-1.06; P = .009). Our findings illustrated the significant causal effect of varicose veins on HF, suggesting that people with varicose veins might have a higher risk of HF. The results provided a novel and important perspective into the development mechanism of HF.

Characterizing stay-green in barley across diverse environments: unveiling novel haplotypes

Key messageThere is variation in stay-green within barley breeding germplasm, influenced by multiple haplotypes and environmental conditions. The positive genetic correlation between stay-green and yield across multiple environments highlights the potential as a future breeding target.Barley is considered one of the most naturally resilient crops making it an excellent candidate to dissect the genetics of drought adaptive component traits. Stay-green, is thought to contribute to drought adaptation, in which the photosynthetic machinery is maintained for a longer period post-anthesis increasing the photosynthetic duration of the plant. In other cereal crops, including wheat, stay-green has been linked to increased yield under water-limited conditions. Utilizing a panel of diverse barley breeding lines from a commercial breeding program we aimed to characterize stay-green in four environments across two years. Spatiotemporal modeling was used to accurately model senescence patterns from flowering to maturity characterizing the variation for stay-green in barley for the first time. Environmental effects were identified, and multi-environment trait analysis was performed for stay-green characteristics during grain filling. A consistently positive genetic correlation was found between yield and stay-green. Twenty-two chromosomal regions with large effect haplotypes were identified across and within environment types, with ten being identified in multiple environments. In silico stacking of multiple desirable haplotypes showed an opportunity to improve the stay-green phenotype through targeted breeding. This study is the first of its kind to model barley stay-green in a large breeding panel and has detected novel, stable and environment specific haplotypes. This provides a platform for breeders to develop Australian barley with custom senescence profiles for improved drought adaptation.

Association between migraine and venous thromboembolism: a Mendelian randomization and genetic correlation study.

Previous observational studies have reported an increased risk of venous thromboembolism (VTE) among individuals with migraine. This study aimed to investigate the causal effect of migraine on the development of VTE, as well as explore the genetic correlation between them. We conducted a two-sample Mendelian randomization (MR) study using publicly available summary statistics from large-scale genome-wide association studies for migraine and VTE. Linkage disequilibrium score regression analysis was performed to estimate the genetic correlation between migraine and VTE. There were several shared risk variants (p-value < 5 × 10-8) between migraine and VTE. Linkage disequilibrium score regression analysis found a significant positive genetic correlation between migraine and VTE. The genetic correlations based on two migraine datasets were 0.208 (se = 0.031, p-value = 2.91 × 10-11) and 0.264 (se = 0.040, p-value = 4.82 × 10-11), respectively. Although main MR analysis showed that migraine was associated with an increased risk of VTE (odds ratio = 1.069, 95% confidence interval = 1.022-1.118, p-value = 0.004), the association attenuated to non-significance when using several other MR methods and using another set of genetic instruments. In addition, evidence of heterogeneity was found. Reverse MR analysis showed VTE was associated with increased risk of migraine with aura (odds ratio = 1.137, 95% confidence interval = 1.062-1.218, p-value = 2.47 × 10-4) with no evidence of pleiotropy and heterogeneity. We showed suggestive evidence indicating an association between migraine and increased risk of VTE. Additionally, we found robust evidence suggesting that VTE is associated with an increased risk of migraine. The positive genetic correlation indicates that migraine and VTE has shared genetic basis. Further investigations will be necessary to address potential sex-specific effects in the analysis.

Estimation of genetic parameters as well as trends for growth traits in Harnali sheep

The current study focussed on the growth traits pertaining to Harnali sheep maintained at Sheep Farm, LUVAS, Hisar and data were recorded from pedigree sheets of 1278 animals. Growth traits considered were birth weight (BW), weaning weight (WW), six-month weight (6MW), yearling weight (YW), and pre-weaning average daily gain (PRWDG) and least-squares means for corresponding traits found to be 3.28±0.02 kg, 12.89±0.07 kg, 17.06±0.06 kg, 24.36±0.06 kg, and 106.74±0.61 g, respectively. Effect of different factors like period of birth, sex of animal and dams’ weight at lambing was studied on growth traits. Except YW, significant effect of period of birth was observed on all the growth traits. Sex had significant influence on BW only however, dams’ weight at lambing affected significantly all the considered growth traits except YW. By leveraging the sire component of variance and covariance from mixed model analysis, the paternal half-sib correlation method was used to estimate genetic as well as phenotypic parameters. Estimates of heritability for BW, WW, 6MW, YW and PRWDG were 0.28±0.07, 0.33±0.07, 0.31±0.07, 0.12±0.04 and 0.27±0.06, respectively. Genetic as well as phenotypic trends for WW and PRWDG were found to be positive. Moderate range of genetic variability at weaning weight and its positive genetic and phenotypic correlations with growth traits specially six month’s weight indicated that genetic improvement could be possible through early selection at weaning weight in Harnali sheep.

Genetic analysis of health traits and their associations with longevity, fertility, production, and conformation traits in Holstein cattle

Health traits have high economic values in dairy cattle breeding, which can cause considerable financial loss through involuntary culling. In this study, fourteen health traits were analyzed, including five composite health traits: reproductive disorders (RD), udder health (UH), digestive disorders (DD), metabolic disorders (MD), locomotory diseases (LD), and nine independent health traits: gestation disorders and peripartum disorders (GDPD), irregular estrus cycle and sterility (IECS), metritis (ME), mastitis (MA), abomasal displacement (AD), enteritis (EN), and ketosis (KE), claw diseases (CD), laminitis complex (LC). This study analysed variance components for health traits through both single and bivariate repeatability animal models. All health traits showed low heritability, ranging from 0.001 to 0.025. Most of health traits in five categories showed negative genetic correlations, ranging from -0.012 (CD and EN) to -0.634 (ME and EN). Strong positive genetic correlations appeared within the same category, ranging from 0.469 (EN and AD) to 0.994 (UH and MA, LD and CD). Furthermore, approximate genetic correlations were evaluated between health traits and routinely collected traits (longevity, fertility, production, and conformation). In general, the low to moderate approximate genetic correlations were estimated between health traits and routinely collected traits. The estimated correlations between health traits and longevity, fertility, production, conformation traits could provide an indirect reference for disease resistance breeding in Holstein cattle.

Distribution, diversity and genetic structure of alders (Alnus lusitanica and A. glutinosa) in Spain

Alders (Alnus spp., Betulaceae) are keystone pioneer species in riparian habitats. In the Mediterranean Basin, where the diploid Alnus glutinosa coexists with the recently discovered tetraploid A. lusitanica, the distribution, diversity and genetic structure of alder species is unknown. The main objectives of this study were to report the distribution of A. glutinosa and A. lusitanica, quantify the local genetic diversity of populations and explore the presence of putative hybrids resulting from the coexistence of A. lusitanica and A. glutinosa individuals in Spain. We assessed 627 individuals from 22 natural alder populations by combining chromosome counts, flow cytometry and microsatellite markers (SSRs) analyses. The ploidy analysis, validated through chromosome counts, revealed the presence of 92 diploid and 535 tetraploid trees from three A. glutinosa and 18 A. lusitanica pure populations, respectively. Notably, no hybrids were detected, not even in Assa, the only population where both species co-occur. The occurrence of mixed ploidy level in alder is reported for the first time in Spain (Assa, Logroño, within the Ebro basin). SSR analysis revealed robust genetic differentiation between the two species and distinctive patterns of variation within A. glutinosa. The high level of differentiation observed was supported by the most probable population clustering determined through pca and structure analyses, along with the identification of a high number of private alleles. For A. lusitanica, the results revealed three distinct genetic groups, geographically distributed. Positive genetic and geographical distance correlations indicated that differentiation could have been driven by isolation by distance. In light of the results, A. lusitanica is the most representative, widespread and genetically variable alder species in Spain, and A. glutinosa is restricted to the north-east of the country. The Ebro riverbank is a contact zone between A. lusitanica and A. glutinosa species, in which no evidence of hybridization was detected yet. Finally, with focus on management, our findings may suggest considering A. lusitanica as a new species, which should be regulated by the forest reproductive material legislation.

OA01 Cluster medicine: the role of genetics for identifying shared biological pathways between rheumatoid arthritis and common comorbidities for targeting treatments

Abstract Background/Aims Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with significant pain and disability, as well as increased risk of comorbidities. These comorbidities, such as coronary artery disease, stroke, heart failure and type 2 diabetes, often form predictable clusters highlighting the importance of common disease mechanisms. Identifying these clusters, and the underlying shared mechanisms, is key to the concept of cluster medicine which aims to take a more systemic approach to treating comorbidity. It is hypothesised that inflammatory processes in RA promote the pathogenesis of these comorbid diseases, which typically occur at an earlier stage of life than in the general population. However, few studies have investigated the degree of shared genetic susceptibility implicated across these traits. The present study aimed to identify and characterise pleiotropic loci and shared biological pathways involved in the pathogenesis of RA and cardiometabolic disorders. Methods European-only GWAS summary statistics were collected for RA (seropositive, seronegative, and overall) and seven cardiometabolic traits, including ischemic stroke, any stroke, heart failure, coronary artery disease, hypertension, atrial fibrillation, and type 2 diabetes. Cross-trait linkage disequilibrium score regression was employed to estimate the degree of genetic correlation (rg) between all pairs of traits. Subset-based meta-analysis was performed using the R package ASSET to identify pleiotropic single nucleotide polymorphisms (SNPs). Pleiotropic SNPs were assigned to genes based on positional and eQTL mapping. Prioritised genes were tested for over-representation in functional categories and biological pathways in gene sets obtained from MsigDB and WikiPathways using the hypergeometric test loci. Gene mapping and enrichment analyses were conducted in FUMA. Results RA showed significant positive genetic correlation with all cardiometabolic traits, with the seronegative subtype showing greater correlation than the seropositive subtype. Correlations between RA and cardiometabolic phenotypes ranged from 0.11 - 0.38, the strongest of which was between seronegative RA and heart failure (rg = 0.38, P = 2.6e-07). A total of 67 lead SNPs were identified as potentially pleiotropic. Pleiotropic SNPs were mapped to genes including IL6R, PTPN11, ATXN2, PLCL1 and SOX6. Pathway enrichment analyses revealed that mapped genes were primarily involved in inflammatory signalling pathways, involving interleukins, TNF-α and interferon (gamma and alpha) response. Conclusion This study provides evidence for pleiotropy across RA and cardiometabolic traits, whereby inherited genetic variants predispose to aberrant cytokine signalling, thus conferring risk to multiple diseases where inflammation is a key driver of pathogenesis. Disclosure M. Stoves: None. M. Soomro: None. S. Zhao: None. D. Plant: None. A. Barton: None. J. Bowes: None.

The Estimation of Genetic Parameters for Chronic Progressive Lymphedema and Body Traits in the Rhenish German Draught Horse.

Chronic progressive lymphedema (CPL) is a prevalent and progressive disease in Rhenish German draught horses. The objective of our follow-up study was to evaluate the heritability of this disease in Rhenish German draught horses using pedigree-based and genomic relationship matrices. We employed linear and threshold animal models. Models included the random animal effect and effects of breeding association, coat colour, sex, and age within sex, and farm-related factors, on CPL scores. In addition, we estimated heritabilities in models assuming censoring for data when horses were below an age of 1-15 years. The heritabilities of CPL scores across all ages were 0.595 ± 0.131 and 0.482 ± 0.105 in the threshold and linear animal model with pedigree-based relationship matrices, respectively. The restriction of data to horses with a minimum age at examination or accounting for censored data in younger animals showed an increase in heritabilities of CPL scores up to 0.788 ± 0.168 (threshold model) and 0.752 ± 0.153 (linear model) at an age of 7-8 years. Analyses including genomic relationship matrices yielded very similar estimates, but with smaller standard errors than pedigree-based analyses. Heritabilities in threshold models for CPL prevalence (CPL-bin-score) and the number of affected limbs (CPL-bin-sum) were 0.176-0.189 ± 0.061-0.064 and 0.375-0.433 ± 0.164-0.170, respectively. We were able to show moderately to highly positive genetic correlations between the CPL score and cannon bone circumference (0.529-0.825), height at withers (0.338-0.555), and skinfold thickness (0.241-0.517). Using the dichotomous trait for the CPL score and the genomic relationship matrix resulted in corresponding estimates of 0.868, 0.793, and 0.784, respectively. This study showed the great importance of additive genetic variation influencing the expression of chronic progressive lymphedema in Rhenish German draught horses. Therefore, further research is warranted to implement breeding programmes in a small breeding population that exploit the potential of additive genetic differences among animals for reducing the prevalence and severity of lesions of this incurable disease.

Shared Genetic Determinants of Schizophrenia and Autism Spectrum Disorder Implicate Opposite Risk Patterns: A Genome-Wide Analysis of Common Variants.

The synaptic pruning hypothesis posits that schizophrenia (SCZ) and autism spectrum disorder (ASD) may represent opposite ends of neurodevelopmental disorders: individuals with ASD exhibit an overabundance of synapses and connections while SCZ was characterized by excessive pruning of synapses and a reduction. Given the strong genetic predisposition of both disorders, we propose a shared genetic component, with certain loci having differential regulatory impacts. Genome-Wide single nucleotide polymorphism (SNP) data of European descent from SCZ (N cases = 53386, N controls = 77258) and ASD (N cases = 18381, N controls = 27969) were analyzed. We used genetic correlation, bivariate causal mixture model, conditional false discovery rate method, colocalization, Transcriptome-Wide Association Study (TWAS), and Phenome-Wide Association Study (PheWAS) to investigate the genetic overlap and gene expression pattern. We found a positive genetic correlation between SCZ and ASD (rg = .26, SE = 0.01, P = 7.87e-14), with 11 genomic loci jointly influencing both conditions (conjFDR <0.05). Functional analysis highlights a significant enrichment of shared genes during early to mid-fetal developmental stages. A notable genetic region on chromosome 17q21.31 (lead SNP rs2696609) showed strong evidence of colocalization (PP.H4.abf = 0.85). This SNP rs2696609 is linked to many imaging-derived brain phenotypes. TWAS indicated opposing gene expression patterns (primarily pseudogenes and long noncoding RNAs [lncRNAs]) for ASD and SCZ in the 17q21.31 region and some genes (LRRC37A4P, LINC02210, and DND1P1) exhibit considerable variation in the cerebellum across the lifespan. Our findings support a shared genetic basis for SCZ and ASD. A common genetic variant, rs2696609, located in the Chr17q21.31 locus, may exert differential risk regulation on SCZ and ASD by altering brain structure. Future studies should focus on the role of pseudogenes, lncRNAs, and cerebellum in synaptic pruning and neurodevelopmental disorders.

Characterizing the polygenic overlap and shared loci between rheumatoid arthritis and cardiovascular diseases

BackgroundDespite substantial research revealing that patients with rheumatoid arthritis (RA) have excessive morbidity and mortality of cardiovascular disease (CVD), the mechanism underlying this association has not been fully known. This study aims to systematically investigate the phenotypic and genetic correlation between RA and CVD.MethodsBased on UK Biobank, we conducted two cohort studies to evaluate the phenotypic relationships between RA and CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), and stroke. Next, we used linkage disequilibrium score regression, Local Analysis of [co]Variant Association, and bivariate causal mixture model (MiXeR) methods to examine the genetic correlation and polygenic overlap between RA and CVD, using genome-wide association summary statistics. Furthermore, we explored specific shared genetic loci by conjunctional false discovery rate analysis and association analysis based on subsets.ResultsCompared with the general population, RA patients showed a higher incidence of CVD (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.15–1.28). We observed positive genetic correlations of RA with AF and stroke, and a mixture of negative and positive local genetic correlations underlying the global genetic correlation for CAD and HF, with 13 ~ 33% of shared genetic variants for these trait pairs. We further identified 23 pleiotropic loci associated with RA and at least one CVD, including one novel locus (rs7098414, TSPAN14, 10q23.1). Genes mapped to these shared loci were enriched in immune and inflammatory-related pathways, and modifiable risk factors, such as high diastolic blood pressure.ConclusionsThis study revealed the shared genetic architecture of RA and CVD, which may facilitate drug target identification and improved clinical management.

Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke.

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.

Accelerated biological aging as a potential risk factor for rheumatoid arthritis.

Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive. In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels. Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA. In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA.

Investigating the shared genetic architecture between attention-deficit/hyperactivity disorder and risk taking behavior: A large-scale genomewide cross-trait analysis

BackgroundThis study aims to explore the genetic architecture shared between Attention-Deficit/Hyperactivity Disorder (ADHD) and risk behavior. MethodsBased on the latest large-scale Genome-wide association studies (GWAS), we firstly employed Linkage disequilibrium score regression (LDSC) and Local Analysis of Variant Association (LAVA) to investigate the genetic correlation between risk behavior and ADHD. Then, we conducted cross-trait analysis to identified the Pleiotropic loci. Finally, bidirectional Mendelian randomization analysis (MR) was applied to examine the causal relationship. ResultsWe found a significant positive genetic correlation between ADHD and risk-taking behavior (rg = 0.351, p = 6.50E-37). The cross-trait meta-analysis identified 27 significant SNPs shared between ADHD and risk behavior. The most significant locus, located near the CADM2 gene on chromosome 3, had been identified associated with this two trait (pADHD = 3.07E-05 and prisk-taking behavior = 2.47E-30). The same situation can also be observed near the FOXP2 gene on chromosome 7 (rs8180817, pmeta = 5.72E-21). We found CCDC171 gene and other genes played a significant role in ADHD and risk behavior in mRNA level. Bidirectional MR analysis found a causal relationship between them. LimitationThe majority of our data sources were of European origin, which may limit the generalizability of our findings to other ethnic populations. ConclusionThis article reveals in depth the shared genetic structure between ADHD and risk-taking behavior, finding a significant positive genetic correlation between ADHD and risk-taking behavior. Providing insights for the future treatment and management of these two traits.

Estimation of genetic parameters for the implementation of selective breeding in commercial insect production

BackgroundThere is a burgeoning interest in using insects as a sustainable source of food and feed, particularly by capitalising on various waste materials and by-products that are typically considered of low value. Enhancing the commercial production of insects can be achieved through two main approaches: optimising environmental conditions and implementing selective breeding strategies. In order to successfully target desirable traits through selective breeding, having a thorough understanding of the genetic parameters pertaining to those traits is essential. In this study, a full-sib half-sib mating design was used to estimate variance components and heritabilities for larval size and survival at day seven of development, development time and survival from egg to adult, and to estimate correlations between these traits, within an outbred population of house flies (Musca domestica), using high-throughput phenotyping for data collection.ResultsThe results revealed low to intermediate heritabilities and positive genetic correlations between all traits except development time and survival to day seven of development and from egg to adulthood. Surprisingly, larval size at day seven exhibited a comparatively low heritability (0.10) in contrast to development time (0.25), a trait that is believed to have a stronger association with overall fitness. A decline in family numbers resulting from low mating success and high overall mortality reduced the amount of available data which resulted in large standard errors for the estimated parameters. Environmental factors made a substantial contribution to the phenotypic variation, which was overall high for all traits.ConclusionsThere is potential for genetic improvement in all studied traits and estimates of genetic correlations indicate a partly shared genetic architecture among the traits. All estimates have large standard errors. Implementing high-throughput phenotyping is imperative for the estimation of genetic parameters in fast developing insects, and facilitates age synchronisation, which is vital in a breeding population. In spite of endeavours to minimise non-genetic sources of variation, all traits demonstrated substantial influences from environmental components. This emphasises the necessity of thorough attention to the experimental design before breeding is initiated in insect populations.

Heritability, Genetic Advance and Correlation Analysis for Grain Yield and Yield Components of Chickpea (Cicer arietinum L.)

The experiment was performed to evaluate heritability, genetic advance and genetic correlation for grain yield and its components, in F1 populations by line x tester fashion. The results showed that most traits demonstrated high heritability, except for days to maturity (49%), which displayed moderate heritability. The traits like pods per plant (2.848), 100 seed weight (2.772), number of nodules per plant (2.529), grain yield per plant (3.081) and harvest index (3.786) exhibited a significant genetic advance. Grain yield exhibited positive and significant genetic correlations with pods per plant (0.878), root length (0.878), 100 seed weight (0.929), number of nodules per plant (0.913), and harvest index (0.964) but negative correlations with traits like days to maturity (-0.492) and plant height (-0.266). Correlated response analysis highlighted traits that positively influenced grain yield and suggested indirect selection or index selection for improvement.

Genetic parameter estimation and molecular foundation of chicken beak shape

The bird beak is mainly functioned as feeding and attacking, and its shape has extremely important significance for survival and reproduction. In chickens, since beak shape could lead to some disadvantages including pecking and waste of feed, it is important to understand the inheritance of chicken beak shape. In the present study, we firstly established 4 indicators to describe the chicken beak shapes, including upper beak length (UL), lower beak length (LL), distance between upper and lower beak tips (DB) and upper beak curvature (BC). And then, we measured the 4 beak shape indicators as well as some production traits including body weight (BW), shank length (SL), egg weight (EW), eggshell strength (ES) of a layer breed, Rhode Island Red (RIR), in order to estimate genetic parameters of chicken beak shape. The heritabilities of UL and LL were 0.41 and 0.37, and the heritabilities of DB and BC were 0.22 and 0.21, indicating that beak shape was a highly or mediumly heritable. There were significant positive genetic and phenotypic correlations among UL, LL, and DB. And UL was positively correlated with body weight (BW18) and shank length (SL18) at 18 weeks of age in genetics, and DB was positively correlated with BC in terms of genetics and phenotype. We also found that layers of chicken cages played a role on beak shape, which could be attributed to the difference of lightness in different cage layers. By a genome-wide association study (GWAS) for the chicken UL, we identified 9 significant candidate genes associated with UL in RIR. For the variants with low minor allele frequencies (MAF <0.01) and outside of high linkage disequilibrium (LD) regions, we also conducted rare variant association studies (RVA) and GWAS to find the association between genotype and phenotype. We also analyzed transcriptomic data from multiple tissues of chicken embryos and revealed that all of the 9 genes were highly expressed in beak of chicken embryos, indicating their potential function for beak development. Our results provided the genetic foundation of chicken beak shape, which could help chicken breeding on beak related traits.

A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis.

Obesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links. Summary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits. We found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits. An intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

Evaluation of genetic parameters of growth traits in G2 selected generation of Penaeus monodon

Fifteen whole sib families of the second-generation Penaeus monodon were constructed using artificial mating design in 2020. After labeling the families with fluorescent markers, the growth traits and genetic parameters were evaluated in a cement pond for 56 days. The results showed that the coefficient of variation of growth traits was 11.52-47.53%, indicating a high genetic variation. The heritability range of growth traits of the G2 population of P. monodon was 0.25±0.03-0.41±0.13, which belonged to medium and high heritability, and the statistical test results were significant (P&lt;0.01). The heritability of body length and body weight were 0.38±0.11 and 0.41±0.13, respectively. The evaluation results of genetic correlation among growth traits were highly positive, and the statistical test results were significant (P&lt;0.01). The genetic correlation between body weight and body length was the highest (0.99), and the genetic correlation between the width of the first carapace and the height of the first abdominal segment was the lowest (0.71). The phenotypic correlation between body weight and body length was the highest (0.93), and the lowest was head breastplate width and first abdominal segment height (0.53). These results showed that the G2 generation population of P. monodon has high genetic improvement potential, and the combination of family selection and individual selection achieved better genetic gain. The growth traits were highly positively correlated. Body length and body weight could be selected as the key traits for fast growth line selection, while the other growth traits could be indirectly selected through positive genetic correlation.