Moderate Genetic Correlations Research Articles

Micro-genetic environmental sensitivity across macro-environments of chickens reared in Burkina Faso and France

BackgroundCommercial poultry production systems follow a pyramidal structure with a nucleus of purebred animals under controlled conditions at the top and crossbred animals under commercial production conditions at the bottom. Genetic correlations between the same phenotypes on nucleus and production animals can therefore be influenced by differences both in purebred-crossbred genotypes and in genotype-by-environment interactions across the two environments, known as macro-genetic environmental sensitivity (GES). Within each environment, genotype-by-environment interactions can also occur due to so-called micro-GES. Micro-GES causes heritable variation in phenotypes and decreases uniformity. In this study, genetic variances of body weight (BW) and of micro-GES of BW and the impacts of purebred-crossbred differences and macro-environmental differences on micro-GES of BW were estimated. The dataset contained three subpopulations of slow-growing broiler chickens: purebred chickens (PB) reared in France, and crossbred chickens reared in France (FR) under the same conditions as PB or reared in Burkina Faso (BF) under local conditions. The crossbred chickens were offspring of the same dam line and had PB as their sire line.ResultsEstimates of heritability of BW and micro-GES of BW were 0.54 (SE of 0.02) and 0.06 (0.01), 0.67 (0.03) and 0.03 (0.01), and 0.68 (0.04) and 0.02 (0.01) for the BF, FR, and PB subpopulations, respectively. Estimates of the genetic correlations for BW between the three subpopulations were moderately positive (0.37 to 0.53) and those for micro-GES were weakly to moderately positive (0.01 to 0.44).ConclusionsThe results show that the heritability of the micro-GES of BW varies with macro-environment, which indicates that responses to selection are expected to differ between macro-environments. The weak to moderate positive genetic correlations between subpopulations indicate that both macro-environmental differences and purebred-crossbred differences can cause re-ranking of sires based on their estimated breeding values for micro-GES of BW. Thus, the sire that produces the most variable progeny in one macro-environment may not be the one that produces the most variable offspring in another. Similarly, the sire that produces the most variable purebred progeny may not produce the most variable crossbred progeny. The results highlight the need for investigating micro-GES for all subpopulations included in the selection scheme, to ensure optimal genetic gain in all subpopulations.

PSVII-9 Heterosis Effects on Reproductive Traits in a Multibreed Beef Cattle Herd in Panama

Abstract The aim of this study was to estimate the influence of heterosis and breed percentage on calving interval (CI) and gestation length (GL), and the correlation between age at first calving (AFC) and CI, in beef cows. Data included 1,291 repeated observations of CI and GL from 502 cows with 2,840 individuals in the pedigree, including 3 generations from the multi-breed herd of the livestock experimental station of the Panama Agricultural Innovation Institute (IDIAP) in Gualaca, Panama. The herd was composed of the following genetic groups based on their breed percentage: tropically adapted Brahman (BR), Nellore (Ne), Undefined Bos indicus (BI), Guaymi Creole (CR), Senepol (SP) and Romosinuano (RS); Bos taurus (BT), Simmental (SM), Angus (A), Red Angus (AR), Limousin (LM), Charolais (CH), Wagyu (Wa), and Others (Oth); crossbreeds (cx), Beefmaster (BF), Three CX (F1 x different BT), R1(Backcross BR), R2 (Backcross BT), Composite (combination of at least 4 different breeds with less than 25% of Zebu), Upgrade (87.5% BR 12.5% BT), B1 (62.5% Zebu + 37.5% BT), and B2 (62.5% BT + 37.5% Zebu). The Zebu influenced breed group represents 50.03% of this population, followed by the F1, the three CX, composites, and R1, representing 22%, 13.89%, 6.11%, and 5.34%, respectively. The other breed groups represented less than 2.5% of the population. A repeated records animal model was used to estimate variance components for both CI and GL. A bivariate animal model was used to estimate the genetic correlation between CI and age at first calving (AFC). Fixed effects for all models consisted of contemporary group, age of dam, calf sex, degree of outcross, and breed percentage. Contemporary group was defined by calving year and season of birth. The average CI was 572.6 ± 140 d, with a range of 315 d to 910 d; and the average GL was 284.2 ± 6.3 d. The estimated regression coefficient for CI on heterosis was -0.114 ± 0.10 d/heterosis % (P = 0.266), and for GL was -0.01 ± 0.052 d/heterosis %. A shorter CI was observed for the F1, and three CX, with 558.7 days and 567.2 days, representing a 2.3% and 1.3% reduction in CI, respectively, when compared with the Zebu group. A larger CI was observed for the Nellore and Romosinuano breeds % with 0.17 ± 1.23 d, (P = 0.373) and 0.64± 0.13 d (P = 0.406), respectively. A low heritability (0.037 ± 0.026) for CI was estimated, with a positive genetic trend over the duration of the study. The analysis between CI and AFC revealed a moderate genetic correlation (0.49 ± 0.36) that allows the establishment of a selection program to improve AFC and CI, which would improve the fertility of this multi-breed herd in Panama.

Genetic parameters for calf feeding traits derived from automated milk feeding machines and number of bovine respiratory disease treatments in North American Holstein calves

Precision livestock farming technologies, such as automatic milk feeding machines, have increased the availability of on-farm data collected from dairy operations. We analyzed feeding records from automatic milk feeding machines to evaluate the genetic background of milk feeding traits and bovine respiratory disease (BRD) in North American Holstein calves. Data from 10,076 preweaning female Holstein calves were collected daily over a period of 6 yr (3 yr included per-visit data), and daily milk consumption (DMC), per-visit milk consumption (PVMC), daily sum of drinking duration (DSDD), drinking duration per-visit, daily number of rewarded visits (DNRV), and total number of visits per day were recorded over a 60-d preweaning period. Additional traits were derived from these variables, including total consumption and duration variance (TCV and TDV), feeding interval, drinking speed (DS), and preweaning stayability. A single BRD-related trait was evaluated, which was the number of times a calf was treated for BRD (NTT). The NTT was determined by counting the number of BRD incidences before 60 d of age. All traits were analyzed using single-step genomic BLUP mixed-model equations and fitting either repeatability or random regression models in the BLUPF90+ suite of programs. A total of 10,076 calves with phenotypic records and genotypic information for 57,019 SNP after the quality control were included in the analyses. Feeding traits had low heritability estimates based on repeatability models (0.006 ± 0.0009 to 0.08 ± 0.004). However, total variance traits using an animal model had greater heritabilities of 0.21 ± 0.023 and 0.23 ± 0.024, for TCV and TDV, respectively. The heritability estimates increased with the repeatability model when using only the first 32 d preweaning (e.g., PVMC = 0.040 ± 0.003, DMC = 0.090 ± 0.009, DSDD = 0.100 ± 0.005, DS = 0.150 ± 0.007, DNRV = 0.020 ± 0.002). When fitting random regression models (RRM) using the full dataset (60-d period), greater heritability estimates were obtained (e.g., PVMC = 0.070 [range: 0.020, 0.110], DMC = 0.460 [range: 0.050, 0.680], DSDD = 0.180 [range: 0.010, 0.340], DS = 0.19 [range: 0.070, 0.430], DNRV = 0.120 [range: 0.030, 0.450]) for the majority of the traits, suggesting that RRM capture more genetic variability than the repeatability model with better fit being found for RRM. Moderate negative genetic correlations of -0.59 between DMC and NTT were observed, suggesting that automatic milk feeding machines records have the potential to be used for genetically improving disease resilience in Holstein calves. The results from this study provide key insights of the genetic background of early in-life traits in dairy cattle, which can be used for selecting animals with improved health outcomes and performance.

Familial co-aggregation and shared genetics of cardiometabolic disorders and traits: data from the multi-generational Lifelines Cohort Study

BackgroundIt is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study.MethodsWe used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λR) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h2), shared environment, and genetic correlation (rg) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age2, and sex.ResultsIndividuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λFDR of 1.23 (95% CI 1.20–1.25) for hypertension to λFDR of 2.48 (95% CI 2.15–2.86) for T2D. Most of these were higher than in spouses (λSpouses < λFDR), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h2CRP: 0.26 to h2HDL: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λFDR obesity-MetS: 1.28 (95% CI 1.24–1.32) to λFDR MetS-T2D: 1.61 (95% CI 1.52–1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from rg HDL-Triglycerides: − 0.53 to rg LDL-Apolipoprotein B: 0.94).ConclusionsThere is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.

Genetic parameters for health traits and their association with fertility and milk production in Chinese Holsteins.

Herd health is one of the key problems influencing the efficiency of the dairy industry. Genetic selection, with a focus on animal health, is important for herd improvement. This study aimed to estimate genetic parameters for health traits and their correlations with fertility and milk production traits in dairy cattle. Based on records from 58,549 lactating cows calved between 2015 and 2021, a total of 24 health traits (six composite health traits and 18 independent health traits), four fertility traits and five milk production traits were analysed. First, linear and threshold animal models were used to estimate the variance components and heritabilities of the health traits. Second, a bivariate linear animal model was used to estimate genetic correlations among all 24 health traits. Finally, a bivariate linear animal model based on records from the first lactation was used to estimate the correlations between health traits and fertility or milk production traits. The results showed that all health traits had low heritabilities, ranging from 0.002 (0.001) to 0.048 (0.004) in the linear model and from <0.001 (0.021) to 0.226 (0.035) in the threshold model. Genetic correlations between health traits across categories were generally low, whereas the relatively high genetic correlations were found between health traits within the same category. In this study, only a few significant and moderate genetic correlations were observed between health traits and fertility or milk production traits. Clinical mastitis showed relatively moderate correlations with fertility traits, ranging from 0.277 (0.113) (interval from first to last insemination) to 0.401 (0.104) (calving interval). Moreover, there were moderate genetic correlations between hoof health and milk production traits. The results from the current study will support balanced dairy breeding to genetically improve disease resistance in dairy cows.

Genetic parameters for automatically-measured vaginal temperature, respiration efficiency, and other thermotolerance indicators measured on lactating sows under heat stress conditions

BackgroundGenetic selection based on direct indicators of heat stress could capture additional mechanisms that are involved in heat stress response and enable more accurate selection for more heat-tolerant individuals. Therefore, the main objectives of this study were to estimate genetic parameters for various heat stress indicators in a commercial population of Landrace × Large White lactating sows measured under heat stress conditions. The main indicators evaluated were: skin surface temperatures (SST), automatically-recorded vaginal temperature (TV), respiration rate (RR), panting score (PS), body condition score (BCS), hair density (HD), body size (BS), ear size, and respiration efficiency (Reff).ResultsTraits based on TV presented moderate heritability estimates, ranging from 0.15 ± 0.02 to 0.29 ± 0.05. Low heritability estimates were found for SST traits (from 0.04 ± 0.01 to 0.06 ± 0.01), RR (0.06 ± 0.01), PS (0.05 0.01), and Reff (0.03 ± 0.01). Moderate to high heritability values were estimated for BCS (0.29 ± 0.04 for caliper measurements and 0.25 ± 0.04 for visual assessments), HD (0.25 ± 0.05), BS (0.33 ± 0.05), ear area (EA; 0.40 ± 0.09), and ear length (EL; 0.32 ± 0.07). High genetic correlations were estimated among SST traits (> 0.78) and among TV traits (> 0.75). Similarly, high genetic correlations were also estimated for RR with PS (0.87 ± 0.02), with BCS measures (0.92 ± 0.04), and with ear measures (0.95 ± 0.03). Low to moderate positive genetic correlations were estimated between SST and TV (from 0.25 ± 0.04 to 0.76 ± 0.07). Low genetic correlations were estimated between TV and BCS (from − 0.01 ± 0.08 to 0.06 ± 0.07). Respiration efficiency was estimated to be positively and moderately correlated with RR (0.36 ± 0.04), PS (0.56 ± 0.03), and BCS (0.56 ± 0.05 for caliper measurements and 0.50 ± 0.05 for the visual assessments). All other trait combinations were lowly genetically correlated.ConclusionsA comprehensive landscape of heritabilities and genetic correlations for various thermotolerance indicators in lactating sows were estimated. All traits evaluated are under genetic control and heritable, with different magnitudes, indicating that genetic progress is possible for all of them. The genetic correlation estimates provide evidence for the complex relationships between these traits and confirm the importance of a sub-index of thermotolerance traits to improve heat tolerance in pigs.

Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using Whole-Exome Sequencing.

Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole-exome sequencing (WES). This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti-citrullinated protein antibody (ACPA-) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole-exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA- PR and ACPA+ PR. Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA-. We identified 8 novel loci (in the ACPA- PR group: ZNF503, RPS6KL1, HOMER3, HLA-DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA- PR group: HLA-DRB1*0803 and HLA-DQB1; in the ACPA+ PR group: HLA-DPA1*0401) that were associated with PR and that surpassed genome-wide significance (P < 5 × 10-8 ). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R2 < 0.025), whereas ACPA+ PR and ACPA- PR showed a moderate genetic correlation (0.38 < R2 < 0.8). This study demonstrated the distinct genetic background between ACPA- and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.

A promising resilience parameter for breeding: the use of weight and feed trajectories in growing pigs

BackgroundIncreasing resilience is a priority in modern pig breeding. Recent research shows that general resilience can be quantified via variability in longitudinal data. The collection of such longitudinal data on weight, feed intake and feeding behaviour in pigs has been facilitated by the development of technologies such as automated feeding stations.The goal of this study was to investigate resilience traits, which were estimated as deviations from longitudinal weight, feed intake and feeding behaviour data during the finishing phase. A dataset with 324,207 records between the age of 95 and 155 days on 5,939 Piétrain pigs with known pedigree and genomic information was used. We provided guidelines for a rigid quality control of longitudinal body weight data, as we found that outliers can significantly affect results. Gompertz growth curve analysis, linear modelling and trajectory analyses were used for quantifying resilience traits.ResultsTo our knowledge, this is the first study comparing resilience traits from longitudinal body weight, feed intake and feeding behaviour data in pigs. We demonstrated that the resilience traits are lowly to moderately heritable for deviations in body weight (h2 = 2.9%–20.2%), in feed intake (9.4%–23.3%) and in feeding behaviour (16.2%–28.3%). Additionally, these traits have good predictive abilities in cross-validation analyses. Deviations in individual body weight and feed intake trajectories are highly correlated (rg = 0.78) with low to moderate favourable genetic correlations with feed conversion ratio (rg = 0.39–0.49). Lastly, we showed that some resilience traits, such as the natural logarithm of variances of observed versus predicted body weights (lnvarweight), are more robust to lower observation frequencies and are repeatable over three different time periods of the finishing phase.ConclusionsOur results will help future studies investigating resilience traits and resilience-related traits. Moreover, our study provides first results on standardization of quality control and efficient data sampling from automated feeding station data. Our findings will be valuable for breeding organizations as they offer evidence that pigs’ general resilience can be selected on with good accuracy. Moreover, this methodology might be extended to other species to quantify resilience based on longitudinal data.

Milk coagulation properties are moderately heritable in dairy cows: a meta-analysis using the random-effects model.

This study aimed to conduct a meta-analysis using the random-effects model to merge published genetic parameter estimates for milk coagulation properties (MCP: comprising rennet coagulation time (RCT), curd-firming time (k20), curd firmness 30 min after rennet addition (a30), titrable acidity (TA) and milk acidity or pH) in dairy cows. Overall, 80 heritability estimates and 157 genetic correlations from 23 papers published between 1999 and 2020 were used. The heritability estimates for RCT, a30, k20, TA, and pH were 0.273, 0.303, 0.278, 0.189 and 0.276, respectively. The genetic correlation estimates between RCT-a30, RCT-pH, and RCT-TA were 0.842, 0.549 and -0.565, respectively. Genetic correlation estimates between RCT and production traits were generally low and ranged from -0.142 (between RCT and casein content) to 0.094 (between RCT and somatic cell score). Moderate and significant genetic correlations were observed between a30-pH (-0.396) and a30-TA (0.662). Also, the genetic correlation estimates between a30 and production traits were low to moderate and varied from -0.165 (between a30 and milk yield) to 0.481 (between a30 and casein content). Genetic correlation estimates between pH and production traits were low and varied from -0.190 (between pH and milk protein percentage) to 0.254 (between pH and somatic cell score). The results of this meta-analysis indicated the existence of additive genetic variation for MCP that could be used in genetic selection programs for dairy cows. Because of the moderate heritability of MCP and small genetic correlations with production traits, it could be possible to improve MCP with negligible correlated effects on production traits.

Genetic analysis of protein efficiency and its association with performance and meat quality traits under a protein-restricted diet

BackgroundAn essential component in the development of sustainable pig production is the reduction of nitrogen excretion in fattening pigs. Pig feeds typically contain high levels of dietary crude protein, and due to incomplete conversion to muscle tissue, excess nitrogen is excreted, resulting in environmental problems such as nitrate pollution and greenhouse gas emissions. Therefore, improving protein efficiency (PE), i.e., the proportion of dietary protein that remains in the carcass, is desirable. The aim of this study was to estimate the heritability (h2) of PE and its genetic correlations with phosphorus efficiency, three performance, seven meat quality and two carcass quality traits when pigs were fed a 20% protein-restricted diet, using 1071 Swiss Large White pigs. To determine PE, the intake of feed with known nutrient content was accurately recorded for each pig and the nitrogen and phosphorus content of the carcass was determined using dual-energy X-ray absorptiometry.ResultsWe found an average PE of 0.39 ± 0.04 and a heritability of 0.54 ± 0.10. PE showed a high genetic correlation with phosphorus efficiency (0.61 ± 0.16), moderate genetic correlations with feed conversion ratio (− 0.55 ± 0.14) and average daily feed intake (− 0.53 ± 0.14), and a low genetic correlation with average daily gain (− 0.19 ± 0.19). While PE has favourable genetic correlations with the performance traits and some meat quality traits, there is a potentially unfavourable correlation of PE with meat colour (redness [rg = − 0.27 ± 0.17]; yellowness [rg = − 0.31 ± 0.18]) and intra-muscular fat (IMF; rg = − 0.39 ± 0.15). Feed conversion ratio (FCR) also showed unfavourable genetic correlations with meat lightness, redness yellowness, IMF and cooking loss.ConclusionsPE is a heritable trait that can be considered in breeding programs to reduce the environmental impact of pig production. We found no strong negative correlation of PE with meat quality traits, and that there is potential to indirectly select for improved phosphorus efficiency. Selecting nutrient efficiencies might be a more suitable strategy to reduce nitrogen pollution from manure than focusing on FCR because the latter also shows genetic antagonism with some meat quality traits in our population.

Genomic assessment of early‐onset AD identifies novel risk loci and an incomplete genetic overlap with late‐onset AD

AbstractBackgroundEarly Onset Alzheimer Disease (EOAD, age at onset [AAO] &lt; = 65) is a severe form of AD, often occurring when patients are still caring for children or adults. Despite this, most genetic studies of EOAD have focused on autosomal dominant forms, and there is little understanding of similarities and differences between early and late onset forms of AD (LOAD, [AAO]&gt;65). To address this, we present a genome‐wide association study of non‐Mendelian EOAD and compare it to LOAD GWAS.MethodsPrimary single‐variant analyses were performed using two additive logistic regression for case‐control models (full: SNPs, PCs, sex and APOE‐ɛ4 dosage as covariates; reduced: SNPs and PCs); secondary models included PCs+sex and PCs+APOE. Models were applied on data derived from the Alzheimer Disease Genetics Consortium (ADGC), composed by unrelated individuals. Samples varied from 1293‐1459 cases and 8894‐9366 controls for EOAD, and 8795‐9508 cases and 9702‐10273 controls for LOAD, depending on the considered model. The SNP heritability (h2) and genetic correlation (rg) were estimated using LD score regression. Gene‐based and pathway analysis (gene sets from Msigdb‐v7.0) were performed using FUMA/MAGMA‐v1.6.ResultsWe identified two novel loci associated with EOAD: Chromosome 4 (full model: chr4:102027610, P = 2.98×10−08, near PPP3CA gene) and Chromosome 12 (PCs+sex model: rs117001070, P = 2.11×10−08, intergenic between LINC02444 and LINC02882). We additionally confirmed BIN1 and APOE in the EOAD subset. Several known genes also showed a significant association with LOAD. Heritability analyses showed higher h2 values for EOAD (h2 = 0.29, 0.29, 0.29 and 0.27) than LOAD (h2 = 0.19, 0.16, 0.19, and 0.15), for full, reduced, PCs+sex and PCs+APOE models respectively. Genetic correlation showed moderate but incomplete genetic correlation between EOAD and LOAD. Other than APOE (p = 3.89×10−12), gene‐based tests showed nominal association for EOAD C8orf44‐SGK3 (p = 9.95×10−06), SGK3 (p = 2.01×10−05) and HIST1H2AC (p = 3.04×10−05), and plausible pathways such as HDL remodeling (p = 5.50×10−05) and positive regulation of cholesterol efflux (p = 9.79×10−05). These pathways were nominally associated with LOAD (p = 0.04 and p = 4.05×10−03).ConclusionsWe identified two novel loci associated to EOAD not previously reported by LOAD studies. Heritability and genetic correlation results suggest that the genetic etiology of EOAD has an incomplete genetic overlap with LOAD.

CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice

Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N = 123,509–133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N = 130,684). Because these GWAS implicated the gene CADM2, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort (N = 3,229,317, European; N = 579,623, Latin American; N = 199,663, African American). Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS (“MouseWAS”) by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6–11%), and moderate genetic correlations (rg = 0.20–0.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as TCF4 and PTPRF, and also identified nominal associations proximal to DRD2 and CRHR1. PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.

A Genome-Wide Association Study Meta-Analysis of Alpha Angle Suggests Cam-Type Morphology May Be a Specific Feature of Hip Osteoarthritis in Older Adults.

To examine the genetic architecture of cam morphology using alpha angle (AA) as a proxy measure and conduct an AA genome-wide association study (GWAS) followed by Mendelian randomization (MR) to evaluate its causal relationship with hip osteoarthritis (OA). Observational analyses examined associations between AA measurements derived from hip dual x-ray absorptiometry (DXA) scans from the UK Biobank study and radiographic hip OA outcomes and subsequent total hip replacement. Following these analyses, an AA GWAS meta-analysis was performed (N=44,214) using AA measurements previously derived in the Rotterdam Study. Linkage disequilibrium score regression assessed the genetic correlation between AA and hip OA. Genetic associations considered significant (P < 5 × 10-8 ) were used as AA genetic instrument for 2-sample MR analysis. DXA-derived AA showed expected associations between AA and radiographic hip OA (adjusted odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.58, 1.67]) and between AA and total hip replacement (adjusted hazard ratio 1.45 [95% CI 1.33, 1.59]) in the UK Biobank study cohort. The heritability of AA was 10%, and AA had a moderate genetic correlation with hip OA (rg =0.26 [95% CI 0.10, 0.43]). Eight independent genetic signals were associated with AA. Two-sample MR provided weak evidence of causal effects of AA on hip OA risk (inverse variance weighted OR 1.84 [95% CI 1.14, 2.96], P=0.01). In contrast, genetic predisposition for hip OA had stronger evidence of a causal effect on increased AA (inverse variance weighted β=0.09 [95% CI 0.04, 0.13], P=4.58 × 10-5 ). Expected observational associations between AA and related clinical outcomes provided face validity for the DXA-derived AA measurements. Evidence of bidirectional associations between AA and hip OA, particularly for risk of hip OA on AA, suggests that hip shape modeling secondary to a genetic predisposition to hip OA contributes to the well-established relationship between hip OA and cam morphology in older adults.

Genomic prediction and selection response for grain yield in safflower.

In plant breeding programs, multiple traits are recorded in each trial, and the traits are often correlated. Correlated traits can be incorporated into genomic selection models, especially for traits with low heritability, to improve prediction accuracy. In this study, we investigated the genetic correlation between important agronomic traits in safflower. We observed the moderate genetic correlations between grain yield (GY) and plant height (PH, 0.272-0.531), and low correlations between grain yield and days to flowering (DF, -0.157-0.201). A 4%-20% prediction accuracy improvement for grain yield was achieved when plant height was included in both training and validation sets with multivariate models. We further explored the selection responses for grain yield by selecting the top 20% of lines based on different selection indices. Selection responses for grain yield varied across sites. Simultaneous selection for grain yield and seed oil content (OL) showed positive gains across all sites with equal weights for both grain yield and oil content. Combining g×E interaction into genomic selection (GS) led to more balanced selection responses across sites. In conclusion, genomic selection is a valuable breeding tool for breeding high grain yield, oil content, and highly adaptable safflower varieties.

Genome-wide association study using whole-genome sequencing identifies risk loci for Parkinson’s disease in Chinese population

Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson’s disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (Pcombined = 1.47 × 10−9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P < 5 × 10−8) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient (rb) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P < 0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14–0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations (rg = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD.

Common and rare variant associations with latent traits underlying depression, bipolar disorder, and schizophrenia

Genetic studies in psychiatry have primarily focused on the effects of common genetic variants, but few have investigated the role of rare genetic variants, particularly for major depression. In order to explore the role of rare variants in the gap between estimates of single nucleotide polymorphism (SNP) heritability and twin study heritability, we examined the contribution of common and rare genetic variants to latent traits underlying psychiatric disorders using high-quality imputed genotype data from the UK Biobank. Using a pre-registered analysis, we used items from the UK Biobank Mental Health Questionnaire relevant to three psychiatric disorders: major depression (N = 134,463), bipolar disorder (N = 117,376) and schizophrenia (N = 130,013) and identified a general hierarchical factor for each that described participants’ responses. We calculated participants’ scores on these latent traits and conducted single-variant genetic association testing (MAF > 0.05%), gene-based burden testing and pathway association testing associations with these latent traits. We tested for enrichment of rare variants (MAF 0.05–1%) in genes that had been previously identified by common variant genome-wide association studies, and genes previously associated with Mendelian disorders having relevant symptoms. We found moderate genetic correlations between the latent traits in our study and case–control phenotypes in previous genome-wide association studies, and identified one common genetic variant (rs72657988, minor allele frequency = 8.23%, p = 1.01 × 10−9) associated with the general factor of schizophrenia, but no other single variants, genes or pathways passed significance thresholds in this analysis, and we did not find enrichment in previously identified genes.

Genome-Wide Analysis of Left Ventricular Maximum Wall Thickness in the UK Biobank Cohort Reveals a Shared Genetic Background With Hypertrophic Cardiomyopathy.

Left ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT. We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study. Twenty-one genetic loci were discovered at P<5×10-8. Several novel candidate genes were identified including PROX1, PXN, and PTK2, with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (rg=0.53) and substantial loci overlap (19/21). Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.

Genetic and phenotypic relationships between ewe reproductive performance and wool and growth traits in Uruguayan Ultrafine Merino sheep.

This study reports genetic parameters for yearling and adult wool and growth traits, and ewe reproductive performance. Data were sourced from an Uruguayan Merino flock involved in a long-term selection program focused on reduced fiber diameter (FD), and increased clean fleece weight (CFW) and live weight (LW). Pedigree and performance data from approximately 5,700 mixed-sex yearling lambs and 2,000 mixed-age ewes born between 1999 and 2019 were analyzed. The number of records ranged from 1,267 to 5,738 for yearling traits, and from 1,931 to 7,079 for ewe productive and reproductive performance. Data on yearling and adult wool traits, LW and body condition score (BCS), yearling eye muscle area (Y_EMA), and fat thickness (Y_FAT), and several reproduction traits were analyzed. The genetic relationships between FD and reproduction traits were not different from zero. Moderate unfavorable genetic correlations were found between adult CFW and ewe lifetime reproduction traits (-0.34 ± 0.08 and -0.33 ± 0.09 for the total number of lambs weaned and total lamb LW at weaning, respectively). There were moderate to strong positive genetic correlations between yearling LW and all reproduction traits other than ewe-rearing ability (-0.08 ± 0.11) and pregnancy rate (0.18 ± 0.08). The genetic correlations between Y_EMA and reproduction traits were positive and ranged from 0.15 to 0.49. Moderate unfavorable genetic correlations were observed between yearling FD and Y_FAT and between adult FD and BCS at mating (0.31 ± 0.12 and 0.23 ± 0.07, respectively). The genetic correlations between adult fleece weight and ewe BCS at different stages of the cycle were negative, but generally not different from zero. This study shows that selection for reduced FD is unlikely to have any effect on reproduction traits. Selection for increased yearling LW and Y_EMA will improve ewe reproductive performance. On the other hand, selection for increased adult CFW will reduce ewe reproductive performance, whereas selection for reduced FD will negatively impact body fat levels. Although unfavorable genetic relationships between wool traits and both FAT and ewe reproductive performance existed, simultaneous improvements in the traits would occur using appropriately designed indexes.

Genetic parameters for pulmonary arterial pressure, yearling performance, and carcass ultrasound traits in Angus cattle.

Pulmonary arterial pressure (PAP) can be used as an indicator of susceptibility to pulmonary hypertension and subsequent potential to develop right-sided heart failure (RHF). Previously reported heritability estimates of PAP have been moderate to high. Based on these estimates, selection for the indicator trait, PAP, could reduce the incidence of RHF due to hypoxia. Previous studies have also speculated that increased growth rates and body fat accumulation contribute to increased PAP and RHF. Research evaluating the genetic relationships between PAP and performance traits (e.g., yearling weight and postweaning gain) has yielded conflicting results, leading to ambiguity and uncertainty regarding the underlying genetic relationships. Additionally, no previous research has evaluated the relationship between PAP and ultrasound carcass traits. Therefore, the objective of this study was to estimate trait heritabilities and genetic correlations between PAP, post-weaning growth traits, and ultrasound carcass traits in Angus cattle, using data (n = 4,511) from the American Angus Association. We hypothesized that traits associated with increased growth and muscle would have a positive genetic (i.e., unfavorable) relationship with PAP. Estimates for heritability and genetic correlations were obtained using a multi-trait animal model. Heritability estimates for PAP (0.21 ± 0.04), post-weaning gain (PWG; 0.31 ± 0.04), and yearling weight (YWT; 0.37 ± 0.04) were within the range of estimates previously reported. Genetic correlations were weak (< 0.20) between PAP, PWG, and YWT. A low-to-moderate genetic correlation between PAP and ultrasound ribeye area (UREA) was found (0.25 ± 0.12). Genetic correlations between PAP, ultrasound back fat (UBF), ultrasound intramuscular fat (IMF), and ultrasound rump fat (RUMP) were weak (ranging in magnitude from -0.05 to 0.10) and therefore, do not provide strong support for the hypothesis of an antagonistic relationship between PAP and carcass ultrasound traits, while heritability estimates for UBF (0.43 ± 0.05), UREA (0.31 ± 0.04), IMF (0.35 ± 0.04), and RUMP (0.47 ± 0.05) were in the range of previously reported values.

Estimating genetic gains for tolerance to stress combinations in tropical maize hybrids.

Maize is a strategic food crop in sub-Saharan Africa. However, most maize growing tropical savannas particularly in West and Central African experience the occurrence of frequent droughts and Striga infestation, resulting in 30-100% yield losses. This production zones need maize cultivars that combine tolerance to the two stresses. IITA in collaboration with national partners has thus employed a sequential selection scheme to incorporate both drought tolerance and Striga resistance in topical maize hybrids using reliable screening protocols. The main objective of the present study was therefore to use grain yield and other agronomic traits recorded in regional collaborative hybrid trials conducted for 8years under manged stressful and non-stressful conditions and across rainfed field environments to estimate genetic gains in grain yields using mixed model analyses. The results showed significant (p < 0.05) annual yield gains of 11.89kgha-1 under manged drought stress (MDS) and 86.60kgha-1 under Striga infestation (STRIN) with concomitant yield increases of 62.65kgha-1 under full irrigation (WW), 102.44kgha-1 under Striga non-infested (STRNO) conditions and 53.11kgha-1 across rainfed field environments. Grain yield displayed significant but not strong genetic correlation of 0.41 ± 0.07 between MDS and STRIN, indicating that gene expression was not consistent across the two stress conditions. Furthermore, grain yield recorded in MET had significant moderate genetic correlations of 0.58 ± 0.06 and 0.44 ± 0.07It with MDS and STRIN, respectively. These results emphasize the need to screen inbred linens under both stress conditions to further enhance the rate of genetic gain in grain yield in hybrids for areas where the two stresses co-occur. Nonetheless, this study demonstrated that the sequential selection scheme has been successful in generating hybrids with dependable yields that can reduce chronic food deficits in rural communities experiencing simultaneous presence of drought and S. hermonthica infestation in their production fields.