Positive Genetic Correlations Research Articles

Genetic Variability and Diversity in Red Onion (Allium cepa L.) Genotypes: Elucidating Morpho-Horticultural and Quality Perspectives

Onion (Allium cepa L.) is a prominent spice and vegetable crop farmed commercially worldwide. Variability is viewed as a key signal for any red onion enhancement effort. The current study was, therefore, carried out to learn about genetic variability and diversity among selected genotypes of 20 red onions at the C Block Farm, Bidhan Chandra Krishi Viswavidyalaya, India, during the winter (rabi) season of 2021–2022, in Randomized Complete Block Design (RCBD) with three replications. The characters, viz., average weight of bulbs (kg), neck thickness (cm), total soluble solids (°Brix), total sugar (%), and reducing sugar (%) demonstrated high heritability (97.38–99.97%) coupled with high genetic gain. Such traits were the least influenced by environmental effects, and additive gene action played a pivotal role in the manifestation of such characters. Traits with high heritability values (51.37–67.94%) demonstrate that the observed variability was under genetic control and provide an enormous range of possibilities for accomplishing selection depending on their phenotypic performances. For traits with moderate heritability, viz., bolting (%) and doubling (%), selection would be less effective but can still be given great importance. Based on correlation analysis, the character’s neck thickness, equatorial diameter, and polar diameter unveiled highly positive genetic correlation with the average weight of bulbs (0.120, 0.112; 0.194, 0.210 and 0.120, 0.112 for phenotypic and genotypic correlation coefficient values, respectively), which indicates that the average weight of a bulb would be increased by an increase in such components. According to path coefficient analysis, the equatorial diameter exhibited the most positive direct effect on the average weight of bulbs (0.968), followed by polar diameter (0.687) and neck thickness (0.159). A wide range of variations for qualitative traits, including foliage colour, leaf width, foliage behaviour, the degree of leaf waxiness, the shape of the bulb, and bulb skin colour were observed. Based on Mahalanobish D2 analysis, the genotypes were divided into four clusters. The highest number of genotypes was found in cluster I (eleven), followed by cluster IV (six genotypes) and cluster II (two genotypes). Cluster III had a single genotype and was monogenic. The study confirmed that a wide genetic variation prevailed in the onion genotypes taken under study, which could thereby be utilized in breeding programmes.

Genetic Correlations between Migraine and Carpal Tunnel Syndrome.

Surgical deactivation of extracranial nerve trigger sites is now well established as an effective treatment for migraine headache. Parallels have been drawn to median nerve decompression for carpal tunnel syndrome (CTS), and 2 previous studies have demonstrated an association between migraine and CTS. The authors sought to (1) substantiate these findings in a considerably larger UK cohort, and (2) investigate potential genetic associations between the 2 disorders. Nested case-control studies were conducted in the UK Biobank cohort of 401,656 individuals. Odds ratios were calculated for the association between migraine and CTS in the overall cohort and sex-stratified subsets. Genetic correlation between migraine and CTS was interrogated by linkage disequilibrium score regression, leveraging data from published genomewide association studies. Regions of genetic overlap were identified by multitrait analysis of genomewide association studies and cross-phenotype association. Migraine and CTS show a significant epidemiologic association within UK Biobank (OR, 1.14, 95% CI, 1.04 to 1.25; P = 0.0058), which is specific to women (OR, 1.15; 95% CI, 1.04 to 1.28; P = 0.0057) and not men (OR, 1.07; 95% CI, 0.82 to 1.40; P = 0.61). Genetic analysis demonstrated a significant positive genetic correlation between the 2 disorders ( rg = 0.13; P = 0.0039), and implicated the TRIM32 locus on chromosome 9 as a region of genetic overlap. This study replicates past reports of an epidemiologic association between CTS and migraine, albeit in women only. This association is underpinned by a genetic correlation, with shared genetic susceptibility at the TRIM32 locus. The authors' data add credibility to the notion that an element of entrapment neuropathy underlies migraine pathophysiology. Risk, III.

CORRELATIONS AMONGST TRAITS OF ECONOMIC IMPORTANCE IN LAYER TYPE CHICKENS UNDER RECIPROCAL RECURRENT SELECTION

The objective of this study was to estimate genetic and phenotypic correlations amongst traits in layer type chickens under reciprocal recurrent selection. Matings within pure male line and female lines were carried out to produce purebred male line (AA x AA) and female line (BB x BB). A total of 364 pullets arising from 207 hens and 23 cocks in generation 1 and 440 pullets from 70 hens and 10 cocks in generation 2 under selection were monitored in individual cage units for part period egg production up to 280 days. Parameters considered were age at sexual maturity (ASM), body weight at 20 and 40 weeks (BW 20 and BW40), egg weight average (EWTAV) and egg production up to 280 days (Egg 280). Results obtained shows that ASM had a high negative genetic (-0.52 to -0.64) and moderate phenotypic (-0.39 to -0,46) correlations with BW20 in the male line, positive genetic and phenotypic correlations with EWTAV in both male (0.41 to 0.80 and 0.07 to 0.26) and female line (0.53 and 0.09 to 0.14) and negative genetic and phenotypic correlations in both male (0.45 to -0.65 and -0.08 to -0.53) and female (-0.37 and -0.20), lines, respectively. Similarly, BW40 had positive genetic and phenotypic correlations (0.68 to 0.93 and 0.01 to 0.20) with Egg-280 in the female line. EWTAV had a negative genetic and phenotypic correlation with Egg280 in both male (-0.53 to -0.96 and -0.09 to -0.17) and female line (-0.15 to -0.27 and -0.09 to -0.15), respectively. It was concluded that the favourable correlations that exist between traits measured in this study for both male and female lines indicate the presence of non-additive genetic effects which can be utilized through selection and crossing for commercial use.

Genetic correlations between suicide attempts and psychiatric and intermediate phenotypes adjusting for mental disorders.

Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders. To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes. Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased. These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.

Genome-wide association study reveals growth-related SNPs and candidate genes in grass carp (Ctenopharyngodon idella)

In China, the grass carp (Ctenopharyngodon idella) is a highly significant freshwater fish species. Enhancing growth-related traits can boost output, decrease costs, and accelerate the production of market-ready fish. In this study, the 21 K grass carp array was used to genotype 365 grass carp individuals, identifying 18,161 high-quality single nucleotide polymorphisms (SNPs) across 24 chromosomes. A genome-wide association study (GWAS) was conducted to detect SNPs and genes potentially associated with growth traits, including body height, body depth, body length, and body weight. We identified a strong positive genetic correlation (0.997–0.999) and a moderate to high heritability (0.421–0.501) among the three growth performance traits (body height, body depth, and body weight). Five SNPs, located on four chromosomes (LG01, LG05, LG07, and LG22), were identified as associated with growth-related traits. The proportion of phenotypic variance explained by these SNPs ranged from 6.3 to 13.5% for the growth-related traits. Two of these SNPs were associated with all traits, except body length. Additionally, 98 genes were annotated by the identified SNPs. Most of the candidate genes were known to be involved in muscle growth and bone development. Gene ontology enrichment analysis suggested that terms related to metabolic process and skeletal system morphogenesis were significantly enriched. This study offers insights into the genetic architecture of growth-related traits and provides effective molecular markers for future genome-wide selection breeding of grass carp.

Additional Evidence for the Relationship between Type 2 Diabetes Mellitus and Stroke through Observational and Genetic Analyses.

While type 2 diabetes mellitus (T2DM) is commonly considered a putative causal risk factor for stroke, the effect of stroke on T2DM remains unclear. The intrinsic link underlying T2DM and stroke has neither been thoroughly examined. We aimed to evaluate the phenotypic and genetic relationships underlying T2DM and stroke. We evaluated phenotypic associations using data from the UK Biobank (N=472,050). We then investigated genetic relationships leveraging genomic data in European ancestry for T2DM, with and without adjusting for body mass index (BMI) (T2DM: Ncase/Ncontrol=74,124/824,006; T2DMadjBMI: Ncase/Ncontrol=50,409/523,897), and for stroke (Ncase/Ncontrol=73,652/1,234,808). We performed additional analyses using genomic data in East Asian ancestry for T2DM (Ncase/Ncontrol=77,418/356,122) and for stroke (Ncase/Ncontrol=27,413/237,242). Observational analyses suggested a significantly increased hazard of stroke among individuals with T2DM (hazard ratio 2.28 [95%CI 1.97, 2.64]), but a slightly increased hazard of T2DM among individuals with stroke (1.22 [1.03, 1.45]) which attenuated to 1.14 [0.96, 1.36] in sensitivity analysis. A positive global T2DM-stroke genetic correlation was observed (rg=0.35; P=1.46×10-27), largely independent of BMI (T2DMadjBMI-stroke: rg=0.27; P=3.59×10-13). This was further corroborated by 38 shared independent loci and 161 shared expression-trait associations. Mendelian randomization analyses suggested a putative causal effect of T2DM on stroke in Europeans (odds ratio 1.07 [95%CI 1.06, 1.09]), which remained significant in East Asians (1.03 [1.01, 1.06]). Conversely, despite a putative causal effect of stroke on T2DM also observed in Europeans (1.21 [1.07, 1.37]), it attenuated to 1.04 [0.91, 1.19] in East Asians. Our study provides additional evidence to underscore the significant relationship between T2DM and stroke.

Is adjustment disorder genetically correlated with depression, anxiety, or risk-tolerant personality trait?

Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of conduct. The disorder is moderately heritable and has lifetime comorbidities with major depressive disorder (MDD), anxiety disorders, or risk-tolerant personality. However, it remains unclear whether the degrees of genetic correlations between adjustment disorder and other psychiatric disorders and intermediate phenotypes are similar or different to those between MDD, anxiety disorders or risk-tolerant personality and these other psychiatric disorders and intermediate phenotypes. To compare patterns of genetic correlations, we utilized large-scale genome-wide association study summary statistics for adjustment disorder-related disorders and personality trait, eleven other psychiatric disorders and fifteen intermediate phenotypes. Adjustment disorder had highly positive genetic correlations with MDD, anxiety disorders, and risk-tolerant personality. Among other psychiatric disorders, adjustment disorder, MDD, anxiety disorders and risk-tolerant personality were positively correlated with risks for schizophrenia (SCZ), bipolar disorder (BD), SCZ + BD, attention-deficit/hyperactivity disorder, and cross disorders. In contrast, adjustment disorder was not significantly correlated with risks for obsessive-compulsive disorder, Tourette syndrome, or posttraumatic stress disorder despite significant genetic correlations of MDD or anxiety disorders with these disorders. Among intermediate phenotypes, adjustment disorder, MDD, anxiety disorders, and risk-tolerant personality commonly had a younger age at first sexual intercourse, first birth, and menopause, lower cognitive ability, and higher rate of smoking initiation. Adjustment disorder was not genetically correlated with extraversion, although the related disorder and personality were correlated with extraversion. Only adjustment disorder was correlated with a higher smoking quantity. These findings suggest that adjustment disorder could share a genetic etiology with MDD, anxiety disorders and risk-tolerant personality trait, as well as have a disorder-specific genetic etiology.

Multi‐trait genomic predictions using GBLUP and Bayesian mixture prior model in beef cattle

AbstractMultiple trait genomic selection incorporating correlated traits can improve the predictive ability of low‐heritability traits. In this study, we evaluated genomic prediction accuracy using multi‐trait BayesCπ method (MT‐BayesCπ), which allows for a broader range of mixture priors for important traits in beef cattle. We compared the prediction performance of MT‐BayesCπ with single‐trait genomic best linear unbiased prediction (ST‐GBLUP), multi‐trait GBLUP (MT‐GBLUP), and single‐trait BayeCπ (ST‐BayesCπ) methods. We found that ribeye area (REA) and ribeye weight (REWT) showed high heritability, while slaughter weight (SWT) and carcass weight (CWT) displayed medium heritability, and slaughter rate (SR) and feedlot average daily gain (FDG) showed low heritability. Highly positive genetic correlations were observed between CWT and SWT (0.981) and SR and REWT (0.921). Notably, the MT‐BayesCπ method showed superior predictive abilities compared to other models. Using MT‐BayesCπ method, the accuracy increased from 0.272 to 0.694 for CWT compared to ST‐GBLUP and ST‐BayesCπ. MT‐GBLUP and ST‐BayesCπ showed similar prediction accuracies, while MT‐BayesCπ showed the least biased evaluations. Additionally, our results suggested that prediction accuracy of low‐heritability traits significantly increased when they were combined with traits with high genetic correlation in a multi‐trait prediction. Our study suggests that multi‐trait genomic predictions using GBLUP and Bayesian mixture prior models is feasible for genomic selection in beef cattle. Our findings indicate that MT‐BayesCπ outperforms other models (ST‐GBLUP, MT‐GBLUP and ST‐BayesCπ), especially for low‐heritability traits.

Comparison of non-linear models and genetic parameter estimation for growth curve traits in the Murciano-Granadina goat breed

In this study, we analyzed 50,238 records of the body weight of the Murciano-Granadina goat breed from birth to 360 days of age. The data were collected from a private dairy farm located in Ghale-Ganj city, which is in the southern part of Kerman province, in the south of Iran. The records were collected between 2016 and 2022. Our goal was to evaluate the suitability of non-linear models for characterizing growth curves from birth to 360 days of age and to estimate genetic parameters for these growth curve traits. Five non-linear mathematical models namely Brody, Negative exponential, von Bertalanffy, Logistic, and Gompertz were compared by using Akaike's information criterion (AIC), root mean square error (RMSE), and Durbin-Watson statistic (DW) to determine the most suitable function for characterizing the growth curve. Among the investigated models, the von Bertalanffy model exhibited the lowest values for both AIC and RMSE. Additionally, we observed positive autocorrelations among residuals for all of the investigated non-linear models, with the lowest value being observed for the von Bertalanffy model. As a result, we selected the von Bertalanffy as the most suitable model for characterizing the growth curve of the Murciano-Granadina goat breed. To estimate genetic parameters for the growth curve traits, including parameters A (estimated mature weight), B (an integration constant related to initial animal weight), K (maturation rate), inflection age (IA), and inflection weight (IW), we utilized a Bayesian multivariate animal model that accounted only for direct additive genetic effects. The posterior means for heritabilities of A, B, K, IA, and IW were significant values of 0.11, 0.13, 0.03, 0.11, and 0.17, respectively. Parameter A had significant and positive genetic and phenotypic correlations with parameters B, IA, and IW. The posterior means for genetic and phenotypic correlations between parameters A and K were negative estimates of − 0.58 and − 0.17, respectively, implying that the kids with slower maturation rates had higher mature weights. Positive and medium estimates were obtained for posterior means of phenotypic (0.04) and genetic (0.29) correlations between parameters B and K. Both posterior means for phenotypic and genetic correlations of B with IA were 0.32 while those of B with IW were 0.51 and 0.50, respectively. We found high and positive genetic (0.51) and phenotypic (0.50) correlations between IA and IW. However, we observed low levels of additive genetic variation for all of the studied growth curve traits. In conclusion, our analysis suggests that the growth curve traits of the Murciano-Granadina goat breed are highly influenced by non-additive genetic and environmental effects. Therefore, it is essential to consider these effects when designing strategies to improve these traits and develop an appropriate breeding scheme that can achieve the desired shape of the growth curve.

Identification of loci involved in childhood visual acuity and associations with cognitive skills and educational attainment.

Visual acuity significantly contributes to quality of life. Deficits in childhood are associated with reading difficulties, which can have detrimental effects on education outcomes. In adults, it has been observed that vision defects such as myopia are associated with higher educational attainment (EA). Understanding genetic factors contributing to visual acuity could help to dissect its links with cognitive skills, neurodevelopmental conditions, and education. We examined associations between distance visual acuity, cognitive measures including school grades, and neurodevelopmental conditions in a longitudinal cohort of British children (ALSPAC, n = 6807, M age = 11.8). We performed a genome-wide association study (GWAS, n = 5571) on visual acuity and tested for genetic associations with relevant phenotypes using polygenic scores (PGS) and genetic correlation analyses. Visual acuity was associated with better cognitive performance and school grades, and reduced in individuals with reading difficulties compared to controls. GWAS revealed genetic associations at the NPLOC4 locus and highlighted other genes involved in sensory function. In line with positive genetic correlations between visual acuity and cognitive measures, EA PGS were positively associated with visual acuity, while there was a less robust negative association with myopia PGS. In conclusion, increased visual acuity is associated with a range of positive outcomes, including better school grades. Our results suggest an association between a higher EA PGS and slightly increased visual acuity in childhood. This could indicate gene-environment correlation, in which environmental exposures linked to higher EA might have detrimental effects on vision offsetting the initial positive effect.

Persistent thinness and anorexia nervosa differ on a genomic level

Thinness and anorexia nervosa are both characterised by persistent low weight. Individuals with anorexia nervosa concurrently report distorted perceptions of their body and engage in weight-loss behaviours, whereas individuals with thinness often wish to gain weight. Both conditions are heritable and share genomics with BMI, but are not genetically correlated with each other. Based on their pattern of genetic associations with other traits, we explored differences between thinness and anorexia nervosa on a genomic level. In Part 1, using publicly available data, we compared genetic correlations of persistent thinness/anorexia nervosa with eleven psychiatric disorders. In Part 2, we identified individuals with adolescent persistent thinness in the Avon Longitudinal Study of Parents and Children (ALSPAC) by latent class growth analysis of measured BMI from 10 to 24 years (n = 6594) and evaluated associations with psychiatric and anthropometric polygenic scores. In Part 1, in contrast to the positive genetic correlations of anorexia nervosa with various psychiatric disorders, persistent thinness showed negative genetic correlations with attention deficit hyperactivity disorder (rgAN = 0.08 vs. rgPT = −0.30), alcohol dependence (rgAN = 0.07 vs. rgPT = −0.44), major depressive disorder (rgAN = 0.27 vs. rgPT = −0.18) and post-traumatic stress disorder (rgAN = 0.26 vs. rgPT = −0.20). In Part 2, individuals with adolescent persistent thinness in the ALSPAC had lower borderline personality disorder polygenic scores (OR = 0.77; Q = 0.01). Overall, results suggest that genetic variants associated with thinness are negatively associated with psychiatric disorders and therefore thinness may be differentiable from anorexia nervosa on a genomic level.

Same-sex sociosexual behaviour is widespread and heritable in male rhesus macaques.

Numerous reports have documented the occurrence of same-sex sociosexual behaviour (SSB) across animal species. However, the distribution of the behaviour within a species needs to be studied to test hypotheses describing its evolution and maintenance, in particular whether the behaviour is heritable and can therefore evolve by natural selection. Here we collected detailed observations across 3 yr of social and mounting behaviour of 236 male semi-wild rhesus macaques, which we combined with a pedigree dating back to 1938, to show that SSB is both repeatable (19.35%) and heritable (6.4%). Demographic factors (age and group structure) explained SSB variation only marginally. Furthermore, we found a positive genetic correlation between same-sex mounter and mountee activities, indicating a common basis to different forms of SSB. Finally, we found no evidence of fitness costs to SSB, but show instead that the behaviour mediated coalitionary partnerships that have been linked to improved reproductive success. Together, our results demonstrate that SSB is frequent in rhesus macaques, can evolve, and is not costly, indicating that SSB may be a common feature of primate reproductive ecology.

Dissecting shared genetic architecture between obesity and multiple sclerosis.

Observational studies have associated obesity with an increased risk of multiple sclerosis (MS). However, the role of genetic factors in their comorbidity remains largely unknown. Our study aimed to investigate the shared genetic architecture underlying obesity and MS. By leveraging data from genome-wide association studies, we investigated the genetic correlation of body mass index (BMI) and MS by linkage disequilibrium score regression and genetic covariance analyser. The casualty was identified by bidirectional Mendelian randomisation. Linkage disequilibrium score regression in specifically expressed genes and multimarker analysis of GenoMic annotation was utilised to explore single-nucleotide polymorphism (SNP) enrichment at the tissue and cell-type levels. Shared risk SNPs were derived using cross-trait meta-analyses and Heritability Estimation from Summary Statistics. We explored the potential functional genes using summary-data-based Mendelian randomization (SMR). The expression profiles of the risk gene in tissues were further examined. We found a significantly positive genetic correlation between BMI and MS, and the causal association of BMI with MS was supported (β=0.22, P=8.03E-05). Cross-trait analysis yielded 39 shared risk SNPs, and the risk gene GGNBP2 was consistently identified in SMR. We observed tissue-specific level SNP heritability enrichment for BMI mainly in brain tissues for MS in immune-related tissues, and cell-type-specific level SNP heritability enrichment in 12 different immune cell types in brain, spleen, lung, and whole blood. The expressions of GGNBP2 were significantly altered in the tissues of patients with obesity or MS compared to those of control subjects. Our study indicates the genetic correlation and shared risk genes between obesity and MS. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics. This work was funded by the National Natural Science Foundation of China (82171698, 82170561, 81300279, and 81741067), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), Natural Science Foundation of Guangdong Province (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Programme of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201803, KJ012019099, KJ012021143, and KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Estimation of genetic parameters of pig reproductive traits.

In this study, we aimed to estimate the genetic parameters of the reproductive traits in three popular commercial pig breeds: Duroc, Landrace, and Yorkshire. Additionally, we evaluated the factors that influence these traits. We collected data from a large number of litters, including 1,887 Duroc, 21,787 Landrace, and 74,796 Yorkshire litters. Using the ASReml-R software to analyze 11 traits, which included: total number of pigs born (TNB); number of piglets born alive (NBA); number of piglets born healthy (NBH); number of piglets born weak (NBW); number of new stillborn piglets (NS); number of old stillborn piglets (OS); number of piglets born with malformation (NBM); number of mummified piglets (NM); total litter birthweight (LBW); litter average weight (LAW); duration of gestational period (GP). We investigated the effects of 4 fixed factors on the genetic parameters of these traits. Among the 11 reproductive-related traits, the gestational period belonged to the medium heritability traits (0.251-0.430), while remaining traits showed low heritability, ranging from 0.005 to 0.159. TNB, NBA, NBH, LBW had positive genetic correlation (0.737 ~ 0.981) and phenotype correlation (0.711 ~ 0.951). There was a negative genetic correlation between NBW and LAW (-0.452 ~ -0.978) and phenotypic correlation (-0.380 ~ -0.873). LBW was considered one of the most reasonable reproductive traits that could be used for breeding improvement. Repeatability of the three varieties was within the range of 0.000-0.097. In addition, the fixed effect selected in this study had a significant effect on Landrace and Yorkshire (p < 0.05). We found a positive correlation between LBW and TNB, NBA, and NBH, suggesting the potential for multi-trait association breeding. Factors such as farm, farrowing year, breeding season, and parity should be taken into consideration in practical production, as they may impact the reproductive performance of breeding pigs.

Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis

Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancers can contribute to enhancing our insights into carcinogenesis.

A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis.

Patients with osteoarthritis (OA) are exposed to an increased risk of adverse outcomes of COVID-19, and they tend to experience disruption in access to healthcare services and exercise facilities. However, a deep understanding of this comorbidity phenomenon and the underlying genetic architecture of the two diseases is still unclear. In this study, we aimed to untangle the relationship between OA and COVID-19 outcomes by conducting a large-scale genome-wide cross-trait analysis. Genetic correlation and causal relationships between OA and COVID-19 outcomes (critical COVID-19, COVID-19 hospitalization, and COVID-19 infection) were estimated by linkage disequilibrium score regression and Mendelian Randomization approaches. We further applied Multi-Trait Analysis of GWAS and colocalization analysis to identify putative functional genes associated with both OA and COVID-19 outcomes. Significant positive genetic correlations between OA susceptibility and both critical COVID-19 (rg=0.266, P=0.0097) and COVID-19 hospitalization (rg=0.361, P=0.0006) were detected. However, there was no evidence to support causal genetic relationships between OA and critical COVID-19 (OR=1.17[1.00-1.36], P=0.049) or OA and COVID-19 hospitalization OR=1.08[0.97-1.20], P=0.143). These results were robustly consistent after the removal of obesity-related single nucleotide polymorphisms (SNPs). Moreover, we identified a strong association signal located near the FYCO1 gene (lead SNPs: rs71325101 for critical COVID-19, Pmeta=1.02×10-34; rs13079478 for COVID-19 hospitalization, Pmeta=1.09×10-25). Our findings further confirmed the comorbidity of OA and COVID-19 severity, but indicate a non-causal impact of OA on COVID-19 outcomes. The study offers an instructive perspective that OA patients did not generate negative COVID-19 outcomes during the pandemic in a causal way. Further clinical guidance can be formulated to enhance the quality of self-management in vulnerable OA patients.

Shared Genetic Loci Between Schizophrenia and White Blood Cell Counts Suggest Genetically Determined Systemic Immune Abnormalities.

Immune mechanisms are indicated in schizophrenia (SCZ). Recent genome-wide association studies (GWAS) have identified genetic variants associated with SCZ and immune-related phenotypes. Here, we use cutting edge statistical tools to identify shared genetic variants between SCZ and white blood cell (WBC) counts and further understand the role of the immune system in SCZ. GWAS results from SCZ (patients, n = 53 386; controls, n = 77 258) and WBC counts (n = 56 3085) were analyzed. We applied linkage disequilibrium score regression, the conditional false discovery rate method and the bivariate causal mixture model for analyses of genetic associations and overlap, and 2 sample Mendelian randomization to estimate causal effects. The polygenicity for SCZ was 7.5 times higher than for WBC count and constituted 32%-59% of WBC count genetic loci. While there was a significant but weak positive genetic correlation between SCZ and lymphocytes (rg = 0.05), the conditional false discovery rate method identified 383 shared genetic loci (53% concordant effect directions), with shared variants encompassing all investigated WBC subtypes: lymphocytes, n = 215 (56% concordant); neutrophils, n = 158 (49% concordant); monocytes, n = 146 (47% concordant); eosinophils, n = 135 (56% concordant); and basophils, n = 64 (53% concordant). A few causal effects were suggested, but consensus was lacking across different Mendelian randomization methods. Functional analyses indicated cellular functioning and regulation of translation as overlapping mechanisms. Our results suggest that genetic factors involved in WBC counts are associated with the risk of SCZ, indicating a role of immune mechanisms in subgroups of SCZ with potential for stratification of patients for immune targeted treatment.

Exploiting the Genetic Potential of Cowpea in An Intercropping Complex

In the West African sub-region, intercropping is a critical element in cowpea product profiles. This study aimed to investigate the impact of intercropping cowpea with pearl millet on genetic correlations, heritability, and response to selection. Thirty-five cowpea genotypes and one pearl millet variety were used to create three cropping patterns: sole cowpea, 1:1 (one row of millet to one row of cowpea), and 2:4 (two rows of millet to four rows of cowpea). Split-plot experiments were conducted for two years with cropping patterns considered as the main plots and genotypes as sub-plots. Data were captured on grain yield (GY), 100 seed weight (Hsdwt), pod weight (Pdwt), fodder weight (Fdwt), and harvest index (HI). Genotype, cropping pattern, year, and genotype-by-cropping pattern interactions were significant for most of the traits. Higher heritability and predicted genetic advance were depicted under sole cropping rather than in the intercropped systems. High positive genetic correlations (rg ≥ 0.9) were obtained between cropping patterns. Genetic correlations among traits were higher under sole cropping than in the intercropping. Path analysis portrayed the HI as having the highest significant and positive direct effect on GY. This study identified short duration cowpea genotypes that are stable and adapted to unique cropping systems.

Genetic Analysis of Productive Performance in New Zealand White Rabbits

In this study, the genetic parmeters of the New Zealand white (NZW) rabbit were evaluated and clarified, including heritability and the common-litter effect, as well as genetic, common-litter, phenotypic correlations, and breeding values. For this purpose, 656 rabbits were kept at the Sakha research farm, for two years. A multi-trait animal model was used to analyze the body weights and relative growth rates data. Heritability estimations (h2a) for various body weights ranged from 0.15 to 0.30 and were low to moderate. The minimum estimate of h2a for relative growth rates at 4 to 6 weeks was 0.13, and the maximum estimate of h2a for relative growth rates at 10 to 12 weeks was 0.24. Moderate to high and positive genetic correlation (rg) between body weights, 0.36 to 0.73. rg estimates between relative growth rates ranged from moderate (0.45) to high (0.84) and positive. Common-litter correlation (rc) between body weights ranged from moderate (0.32) to high (0.71) and positive. rc estimates between relative growth rates ranged from moderate (0.43) to high (0.71) and positive. The phenotypic correlation (rp) between body weights was moderate (0.41) to high (0.80) and positive. rp estimates between the relative growth rates were high and positive. The estimated ranges of breeding values were 175.07, 263.89, 299.48, 267.78, and 279.86 for 4, 6, 8, 10, and 12 weeks, respectively. While were 24.56, 27.04, 31.80, 35.14, and 29.28 during the period of 4-6, 6-8, 8-10, 10-12, and 4-12 weeks, respectively.

Intraspecific variation for host immune activation by the spider mite Tetranychus evansi.

Many parasites can interfere with their host's defences to maximize their fitness. Here, we investigated if there is heritable variation in the spider mite Tetranychus evansi for traits associated with how they interact with their host plant. We also determined if this variation correlates with mite fecundity. Tetranychus evansi can interfere with jasmonate (JA) defences which are the main determinant of anti-herbivore immunity in plants. We investigated (i) variation in fecundity in the presence and absence of JA defences, making use of a wild-type tomato cultivar and a JA-deficient mutant (defenseless-1), and (ii) variation in the induction of JA defences, in four T. evansi field populations and 59 inbred lines created from an outbred population originating from controlled crosses of the four field populations. We observed a strong positive genetic correlation between fecundity in the presence (on wild-type) and the absence of JA defences (on defenseless-1). However, fecundity did not correlate with the magnitude of induced JA defences in wild-type plants. Our results suggest that the performance of the specialist T. evansi is not related to their ability to manipulate plant defences, either because all lines can adequately reduce levels of defences, or because they are resistant to them.