Estimates Of Genetic Correlations Research Articles

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.

Genetic correlation estimates between calving ease in primiparous cows and economically important traits in Nellore cattle.

This study aimed to estimate (co)variance components and genetic parameters for calving ease (CE) and their genetic correlations with growth, reproductive, carcass, and feed efficiency traits in Nellore cattle. Phenotypes for CE are scored in two categories: normal calving and assisted calving. The traits considered were probability of precocious calving, age at first calving, stayability, adjusted scrotal circumference at 365 days of age, accumulated cow productivity, age at puberty of males, gestation length, birth weight, adjusted weights at 210 and 450 days of age, adult cow weight, frame score, hip height, rib eye area, subcutaneous backfat thickness, rump fat thickness, intramuscular fat percentage, residual feed intake and dry matter intake. The estimation of genetic parameters was performed using a two-trait threshold-linear animal model, except for CE, stayability, and probability of precocious calving, which were evaluated through a two-trait threshold animal model. The direct (0.27) and maternal (0.19) heritability estimates for CE in heifers primiparous Nellore indicated that selecting for this trait is feasible. The selection to improve the female sexual precocity should consider CE during the selection and mating decisions to reduce calving problems. Genetic correlation estimates between CE and BW suggest that selecting low birth weight to reduce calving problems is not an appropriate strategy to improve calving ease in heifers Nellore. Therefore, adopting a multi-trait selection model with CE and BW in the Nellore breed would reduce calving difficulties, particularly in sexually precocious heifers, without impairing the growth, reproductive, feed efficiency conversion, and carcass indicator traits.

Heritability and genetic correlations of rumination time with milk-yield and milking traits in Holstein-Friesian cows using an automated milking system

Knowledge of the values of genetic parameters is a prerequisite for conducting a breeding program. This is especially important for rumination, which is considered an indicator of cow’s health. Exploring the genetic relations between rumination time, milk yield, and milking traits could make it a valuable tool in dairy cattle breeding strategies. The objective of the research was to estimate heritability, repeatability, and genetic and phenotypic correlations of rumination time (RT), as well as traits associated with milk yield and milking of dairy cows of the Polish Holstein-Friesian breed kept in herds equipped with an automatic milking system. The research takes into consideration daily results for milking in the first lactation and second lactation, from 1 486 cows of the breed milked between 2013 and 2015 year. Cows were housed in 24 free-stall barns and fed a Partial Mixed Ration feed. The barns had an automated milking system (Astronaut A4 – Lely Industry). The cows received a varied dose of the concentrate, either in the milking robot or the feeding station, depending on the level of their milk yield. Our research has shown that RT was a low heritable trait (0.140 ± 0.039) and had a medium repeatability (0.572 ± 0.007). We detected a positive genetic correlation between RT and milk yield (0.341); however, a statistically significant negative relationship was identified between RT and urea content (−0.418) in milk. Estimations of genetic correlations suggest that selecting for higher RT may correspond to reduced urea content in milk. Investigating the genetics aspect of RT and the relationship with milk yield and milking traits may turn this into one of the useful criterion selections for dairy cattle breeding strategies, but should be used carefully. Further analyses on larger data sets and different populations are necessary.

Warm‐season turfgrass species genotype‐by‐environment interaction for turfgrass quality under drought

AbstractOne of the biggest challenges the turfgrass industry is currently facing is limitations of available water for irrigation of turfgrass areas. Efforts on breeding for drought resistance have increased over the past several years across the United States. Thus, the objectives of this study were to evaluate the performance of bermudagrass (Cynodon spp. Rich.), St. Augustinegrass (Stenotaphrum secundatum (Walter) Kuntze), seashore paspalum (Paspalum vaginatum Swartz) and zoysiagrass (Zoysia spp. Willd.) breeding lines from five different breeding programs under drought and estimate genetic parameters in order to increase selection efficiency for drought resistance improvement in these breeding programs. The germplasm sources were bermudagrass from Oklahoma State University and University of Georgia (UGA); St. Augustinegrass from North Carolina State University, Texas A&M University System (TAMUS) and University of Florida (UF); zoysiagrass from UF and TAMUS; seashore paspalum from UGA. Field trials were conducted from 2016 to 2019 at research facilities in Citra, FL and Dallas, TX. The response variables evaluated were per cent living ground cover (%GC), and turfgrass quality under normal or non‐drought (TQND) and drought conditions (TQD). The genetic variance was significant for TQND and TQD in bermudagrass, TQD in St. Augustinegrass and all traits in zoysiagrass. The heritability estimates were higher for TQD than for TQND in bermudagrass and St. Augustinegrass. Genetic correlation estimates showed that indirect selection can be effective to select drought‐resistant genotypes. Several genotypes performed better than all commercial cultivars in both St. Augustinegrass and zoysiagrass.

Evidence of additive genetic variation for major milk proteins in dairy cows: A meta-analysis.

In the past, there have been reports of genetic parameters for milk proteins in various dairy cattle populations. The high variability among genetic parameter estimates has been caused by this. This study aimed to use a random-effects meta-analysis model to compile published estimates of genetic parameter for major milk proteins of α-lactalbumin, β-lactoglobulin, sum of whey proteins, casein, αs1 -casein, αs2 -casein, β-casein, and κ-casein in dairy cows. The study used a total of 140 heritability and 256 genetic correlation estimates from 23 papers published between 2004 and 2022. The estimated range of milk protein heritability is from 0.284 (for α-lactalbumin in milk) to 0.596 (for sum of whey proteins). The genetic correlation estimates between casein and milk yield, milk fat and protein percentages were -0.461, 0.693, and 0.976, respectively (p < 0.05). The genetic correlation estimates between milk proteins expressed as a percentage of milk were significant and varied from 0.177 (between β-lactoglobulin and κ-casein) to 0.892 (between αs1 -casein and αs2 -casein). Moderate-to-high heritability estimates for milk proteins and their low genetic associations with milk yield and composition indicated the possibility for improving milk proteins in a genetic selection plan with negligible correlated effects on production traits in dairy cows.

Evolutionary relationships between metabolism and behaviour require genetic correlations.

As selection acts on multivariate phenotypes, the evolution of traits within populations not only depends on the genetic basis of each trait, but also on the genetic relationships among traits. As metabolic rate is often related to vital traits such as growth, physiology and behaviour, its variation and evolution is expected to have important repercussions on individual fitness. However, the majority of the correlations between metabolic rate and other traits has been based on phenotypic correlations, while genetic correlations, basis for indirect selection and evolution, have been overlooked. Using a case study, we explore the importance of properly estimating genetic correlations to understand and predict evolution of multivariate phenotypes. We show that selection on metabolic traits could result in indirect selection mainly on growth-related traits, owing to strong genetic correlations, but not on swimming or risk-taking and sociability behaviour even if they covary phenotypically. While phenotypic correlation can inform about genetic correlation direction, caution is needed in predicting the magnitude of genetic correlation. Therefore, even though phenotypic correlations among physiological and behavioural traits could be useful, deriving evolutionary conclusions based purely on them is not robust. In short, proper estimation of genetic correlations is needed when predicting evolutionary consequences. This article is part of the theme issue 'The evolutionary significance of variation in metabolic rates'.

Incorporating body measurement traits to increase genetic gain of feed efficiency and carcass traits in Japanese Black steers.

The objective of the present study was to comprehensively evaluate whether body measurement traits, including body weight and body size, could be used as indicators of genetic selection for feed efficiency and carcass traits in Japanese Black steers. First, we estimated the genetic parameters for body measurements, feed efficiency, and carcass traits. Second, we estimated the correlated responses in feed efficiency and carcass traits when selection was applied to one or multiple-body measurement traits. In total, 4,578 Japanese Black steers with phenotypic values of residual feed intake (RFI) and residual body weight gain (RG) as feed efficiency traits and carcass weight (CWT) and beef marbling standard (BMS) as carcass traits were used. Eleven body measurement traits were measured at the start and finish of the fattening periods (BMT1 and BMT2, respectively), and their growth during the fattening period (BMT3) was used for genetic analyses. The results of genetic parameters showed that the heritability estimates were low to moderate (0.10 to 0.66), and the genetic correlations among body measurement traits were also estimated to be positively moderate to high in each measuring point (0.23 to 0.99). The genetic correlations of body measurement traits with RFI and BMS were estimated to be low (-0.14 to 0.30 and -0.17 to 0.35, respectively), but those with CWT were positively low to high (0.12 to 0.97). The genetic correlation estimates between BMT3 and RG were moderate to high (0.38 to 0.78). Second, correlated responses were estimated under positive selection for body measurement traits. Positive selection for BMT2 and BMT3 increased CWT and RG; however, positive selection for body measurement traits resulted in no change in RFI and BMS. Favorable directions of genetic gains, which were positive for RG, CWT, and BMS and negative for RFI, were obtained by selection indices, including multiple traits in BMT1. Our results suggest that using only one-body measurement trait as an indicator of genetic selection for RFI is difficult. However, body measurement traits can be indirect indicators of improved RG. Our results also suggest that genetic improvement of both RFI and RG without reducing CWT and BMS could be achieved using selection indices that account for a balance of body conformation using multiple-body measurement traits in Japanese Black cattle.

Genotype-by-gestational thermal environment interaction and its impact on the future performance of tropical composite beef cattle offspring.

With global warming, there are growing challenges for raising taurine and composite beef cattle populations in tropical regions, including elevated temperatures, limited forage availability, parasite infestation, and infectious diseases. These environmental factors can trigger specific physiological responses in the developing fetus, which may have long-term implications on its performance. Therefore, the main objective of this study was to assess the influence of naturally induced thermal stress during the gestation period on the subsequent performance of tropical composite beef cattle progeny. Furthermore, we aimed to investigate the impact of genotype-by-gestational thermal environment interaction (G×Eg) on traits under selection pressure in the breeding population. A total of 157,414 animals from 58 farms located in various Brazilian states were recorded for birth weight (BW), preweaning weight gain (PWG), yearling weight (YW), hip height (HH), scrotal circumference (SC), and days to first calving (DFC). We first applied a linear regression model to the BW data, which revealed that the last 40d of gestation were suitable for calculating the mean temperature humidity index (THIg). Subsequent regression analyses revealed that for every 10-unit increase in THIg, detrimental effects of approximately 1.13% to 16.34% are expected for all traits evaluated. Genetic parameters were estimated through a reaction norm model using THIg as the environmental descriptor. The posterior means of heritability estimates (SD) were 0.35 (0.07), 0.25 (0.03), 0.31 (0.03), 0.37 (0.01), 0.29 (0.07), and 0.20 (0.09) for the direct effect of BW, PWG, YW, HH, SC, and DFC, respectively. These estimates varied along the range of THIg values, suggesting a variable response to selection depending on the thermal environment during gestation. Genetic correlation estimates between more divergent THIg values were low or negative for YW, PWG, and DFC, indicating that the best-performing individuals at low THIg values may not perform as well at high THIg values and vice versa. Overall, thermal stress during gestation impacts the future performance of beef cattle offspring. Our results indicate the need for developing effective breeding strategies that take into account G×Eg effects and the re-ranking of breeding animals along the THIg scale, particularly for traits such as DFC that are highly sensitive to thermal stress.

Efeito da idade a primeira concepção como critério de seleção em características de crescimento e carcaça em bovinos Nelore

Abstract The aim was to identify predictive traits of relatively easy measurement and which can be recorded early in life (age at first conception - AFCo), besides estimating its genetic correlations with growth and carcass traits in Nellore cattle. Age at first conception was considered the age at which the female had the first positive diagnosis for pregnancy. The estimation of (co)variance components and genetic parameters was performed using a linear animal model in two-trait analysis. The estimates of heritability were moderate, enabling genetic selection for growth-, carcass-, and sexual precocityrelated traits. The genetic correlation obtained between AFCo and age at first calving (AFCa) was high (0.88), indicating the feasibility of using AFCo as a selection criterion for early calving heifers. Genetic correlation estimates between AFCo and AFCa with weight at 120, 210, 365, and 450 days of age and carcass traits were moderate and negative (-0.33 to -0.62). Thus, genetic selection for animals with early AFCo and AFCa would enhance carcass yield, fat deposition, and growth performance, despite not affecting birth weight or daily weight gain. The results of this study encourage the use of AFCo in Nellore cattle since this trait displayed enough genetic variability in Nellore cattle, and can be used as selection criteria to improve sexual precocity. When the objective of genetic selection is to increase heifer sexual precocity, we could use the first trait as a criterion, as the measurement of this trait occurs at a lower AFCa.

Estimation of Heritability and Genetic Correlation of Quantitative Traits as a Basis for Selection Program of Indonesian Native Chickens

Estimation of Heritability and Genetic Correlation of Quantitative Traits as a Basis for Selection Program of Indonesian Native Chickens

Longitudinal genetic dynamics of weaning index and implications for cow-calf production efficiency

In beef cattle, the selection for higher weights at young ages has been questioned with the argument that this criterion may increase the adult weight of cows, resulting in higher costs. Therefore, selection criteria should be employed to increase weights at young ages with minimal impact on the adult weight of cows. Additionally, the relationship between measures of cow production efficiency and other well-established selection criteria in breeding programs remains poorly understood. The objective of this study was to longitudinally evaluate the relationship between the weaning index (WIndex) as a measure of efficiency and growth traits of the cows. Possible changes over time in WIndex due to selection applied for yearling weight (YW) were also investigated. The WIndex was proposed to maximize genetic response in the weaning weight of the calf while maintaining genetic gain in BW of the cow at zero. A random regression model was adopted to estimate correlations between WIndex, BW, hip height (HH), and body condition score (BCS) using records of Nelore cows from three lines. Genetic trends were calculated for the control line (NeC) and lines selected for greater YW (NeS and NeT). The age of 3 years was the most critical for the weaning efficiency of the cows. At this stage, young cows are still growing and wean lighter calves than their adult counterparts. The genetic correlation estimates between WIndex and BW (−0.58 to 0.04), HH (−0.05 to −0.34), and BCS (−0.51 to −0.17) were close to zero or negative. BW and HH were strongly correlated genetically across all ages (0.73–0.76). In general, HH exhibited a weak and negative genetic relationship with BCS. The genetic correlation between BW and BCS was stronger for advanced ages (0.45–0.68). In lines selected for YW, important increases in WIndex were observed. However, NeS has been selected since the 1980s until the present for YW, and thus, it showed a more pronounced trend of increasing BW and, consequently, a more modest trend of increasing WIndex compared to NeT. In contrast, WIndex exhibited a trend close to zero for NeC. In this context, monitoring HH and BCS can be useful to avoid losses in the weaning efficiency of cows. Furthermore, we suggest that one way to mitigate efficiency losses in calf production could involve stabilizing the BW of cows and increasing the weaning weight of calves using the WIndex.

Longitudinal genomic analyses of automatically-recorded vaginal temperature in lactating sows under heat stress conditions based on random regression models

BackgroundAutomatic and continuous recording of vaginal temperature (TV) using wearable sensors causes minimal disruptions to animal behavior and can generate data that enable the evaluation of temporal body temperature variation under heat stress (HS) conditions. However, the genetic basis of TV in lactating sows from a longitudinal perspective is still unknown. The objectives of this study were to define statistical models and estimate genetic parameters for TV in lactating sows using random regression models, and identify genomic regions and candidate genes associated with HS indicators derived from automatically-recorded TV.ResultsHeritability estimates for TV ranged from 0.14 to 0.20 over time (throughout the day and measurement period) and from 0.09 to 0.18 along environmental gradients (EG, − 3.5 to 2.2, which correspond to dew point values from 14.87 to 28.19 ˚C). Repeatability estimates of TV over time and along EG ranged from 0.57 to 0.66 and from 0.54 to 0.77, respectively. TV measured from 12h00 to 16h00 had moderately high estimates of heritability (0.20) and repeatability (0.64), indicating that this period might be the most suitable for recording TV for genetic selection purposes. Significant genotype-by-environment interactions (GxE) were observed and the moderately high estimates of genetic correlations between pairs of extreme EG indicate potential re-ranking of selection candidates across EG. Two important genomic regions on chromosomes 10 (59.370–59.998 Mb) and16 (21.548–21.966 Mb) were identified. These regions harbor the genes CDC123, CAMK1d, SEC61A2, and NUDT5 that are associated with immunity, protein transport, and energy metabolism. Across the four time-periods, respectively 12, 13, 16, and 10 associated genomic regions across 14 chromosomes were identified for TV. For the three EG classes, respectively 18, 15, and 14 associated genomic windows were identified for TV, respectively. Each time-period and EG class had uniquely enriched genes with identified specific biological functions, including regulation of the nervous system, metabolism and hormone production.ConclusionsTV is a heritable trait with substantial additive genetic variation and represents a promising indicator trait to select pigs for improved heat tolerance. Moderate GxE for TV exist, indicating potential re-ranking of selection candidates across EG. TV is a highly polygenic trait regulated by a complex interplay of physiological, cellular and behavioral mechanisms.

A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

BackgroundThrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient’s prognosis. ObjectivesTo investigate the association between genetically determined natural hemostatic factors’ levels and increased risk of HT after r-tPA treatment. MethodsUsing data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. ResultsLocal correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10−11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10−10; rs1421067 (CHD9), P = 1.81 × 10−14; and rs34780449, near ROBO1 gene, P = 1.64 × 10−8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10−14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [−0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). ConclusionWe identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

Genotype-by-environment interactions for feed efficiency traits in Nellore cattle based on bi-trait reaction norm models

BackgroundSelecting animals for feed efficiency directly impacts the profitability of the beef cattle industry, which contributes to minimizing the environmental footprint of beef production. Genetic and environmental factors influence animal feed efficiency, leading to phenotypic variability when exposed to different environmental conditions (i.e., temperature and nutritional level). Thus, our aim was to assess potential genotype-by-environment (G × E) interactions for dry matter intake (DMI) and residual feed intake (RFI) in Nellore cattle (Bos taurus indicus) based on bi-trait reaction norm models (RN) and evaluate the genetic association between RFI and DMI across different environmental gradient (EG) levels. For this, we used phenotypic information on 12,958 animals (young bulls and heifers) for DMI and RFI recorded during 158 feed efficiency trials.ResultsThe heritability estimates for DMI and RFI across EG ranged from 0.26 to 0.54 and from 0.07 to 0.41, respectively. The average genetic correlations (± standard deviation) across EG for DMI and RFI were 0.83 ± 0.19 and 0.81 ± 0.21, respectively, with the lowest genetic correlation estimates observed between extreme EG levels (low vs. high) i.e. 0.22 for RFI and 0.26 for DMI, indicating the presence of G × E interactions. The genetic correlation between RFI and DMI across EG levels decreased as the EG became more favorable and ranged from 0.79 (lowest EG) to 0.52 (highest EG). Based on the estimated breeding values from extreme EG levels (low vs. high), we observed a moderate Spearman correlation of 0.61 (RFI) and 0.55 (DMI) and a selection coincidence of 53.3% and 40.0% for RFI and DMI, respectively.ConclusionsOur results show evidence of G × E interactions on feed efficiency traits in Nellore cattle, especially in feeding trials with an average daily gain (ADG) that is far from the expected of 1 kg/day, thus increasing reranking of animals.

Genetic analysis of the blood transcriptome of young healthy pigs to improve disease resilience

BackgroundDisease resilience is the ability of an animal to maintain productive performance under disease conditions and is an important selection target. In pig breeding programs, disease resilience must be evaluated on selection candidates without exposing them to disease. To identify potential genetic indicators for disease resilience that can be measured on selection candidates, we focused on the blood transcriptome of 1594 young healthy pigs with subsequent records on disease resilience. Transcriptome data were obtained by 3’mRNA sequencing and genotype data were from a 650 K genotyping array.ResultsHeritabilities of the expression of 16,545 genes were estimated, of which 5665 genes showed significant estimates of heritability (p < 0.05), ranging from 0.05 to 0.90, with or without accounting for white blood cell composition. Genes with heritable expression levels were spread across chromosomes, but were enriched in the swine leukocyte antigen region (average estimate > 0.2). The correlation of heritability estimates with the corresponding estimates obtained for genes expressed in human blood was weak but a sizable number of genes with heritable expression levels overlapped. Genes with heritable expression levels were significantly enriched for biological processes such as cell activation, immune system process, stress response, and leukocyte activation, and were involved in various disease annotations such as RNA virus infection, including SARS-Cov2, as well as liver disease, and inflammation. To estimate genetic correlations with disease resilience, 3205 genotyped pigs, including the 1594 pigs with transcriptome data, were evaluated for disease resilience following their exposure to a natural polymicrobial disease challenge. Significant genetic correlations (p < 0.05) were observed with all resilience phenotypes, although few exceeded expected false discovery rates. Enrichment analysis of genes ranked by estimates of genetic correlations with resilience phenotypes revealed significance for biological processes such as regulation of cytokines, including interleukins and interferons, and chaperone mediated protein folding.ConclusionsThese results suggest that expression levels in the blood of young healthy pigs for genes in biological pathways related to immunity and endoplasmic reticulum stress have potential to be used as genetic indicator traits to select for disease resilience.

Genetic parameters, reciprocal cross differences, and age-related heterosis of egg-laying performance in chickens

BackgroundEgg-laying performance is economically important in poultry breeding programs. Crossbreeding between indigenous and elite commercial lines to exploit heterosis has been an upward trend in traditional layer breeding for niche markets. The objective of this study was to analyse the genetic background and to estimate the heterosis of longitudinal egg-laying traits in reciprocal crosses between an indigenous Beijing-You and an elite commercial White Leghorn layer line. Egg weights were measured for the first three eggs, monthly from 28 to 76 weeks of age, and at 86 and 100 weeks of age. Egg quality traits were measured at 32, 54, 72, 86, and 100 weeks of age. Egg production traits were measured from the start of lay until 43, 72, and 100 weeks of age. Heritabilities and phenotypic and genetic correlations were estimated. Heterosis was estimated as the percentage difference of performance of a crossbred from that of the parental average. Reciprocal cross differences were estimated as the difference between the reciprocal crossbreds as a percentage of the parental average.ResultsEstimates of heritability of egg weights ranged from 0.29 to 0.75. Estimates of genetic correlations between egg weights at different ages ranged from 0.72 to 1.00. Estimates of heritability for cumulative egg numbers until 43, 72, and 100 weeks of age were around 0.15. Estimates of heterosis for egg weight and cumulative egg number increased with age, ranging from 1.0 to 9.0% and from 1.4 to 11.6%, respectively. From 72 to 100 weeks of age, crossbreds produced more eggs per week than the superior parent White Leghorn (3.5 eggs for White Leghorn, 3.8 and 3.9 eggs for crossbreds). Heterosis for eggshell thickness ranged from 2.7 to 6.6% when using Beijing-You as the sire breed. No significant difference between reciprocal crosses was observed for the investigated traits, except for eggshell strength at 54 weeks of age.ConclusionsThe heterosis was substantial for egg weight and cumulative egg number, and increased with age, suggesting that non-additive genetic effects are important in crossbreds between the indigenous and elite breeds. Generally, the crossbreds performed similar to or even outperformed the commercial White Leghorns for egg production persistency.

A comprehensive meta-analysis of genetic parameters for resilience and productivity indicator traits in Holstein cattle

Selection for resilience indicator (RIND) traits in Holstein cattle is becoming an important breeding objective as the worldwide population is expected to be exposed to increased environmental stressors due to both climate change and changing industry standards. However, genetic correlations between RIND and productivity indicator (PIND) traits, which are already being selected for and have the most economic value, are often unfavorable. As a result, it is necessary to fully understand these genetic relationships when incorporating novel traits into selection indices, so that informed decisions can be made to fully optimize selection for both groups of traits. In the past 2 decades, there have been many estimates of RIND traits published in the literature, albeit in small populations. To provide valuable pooled summary estimates, a random-effects meta-analysis was conducted for heritability and genetic correlation estimates for PIND and RIND traits in worldwide Holstein cattle. In total, 926 heritability estimates for 9 PIND and 27 RIND traits, along with 362 estimates of genetic correlation (PIND × RIND traits) were collected. Resilience indicator traits were grouped into the following subgroups: Metabolic Diseases, Hoof Health, Udder Health, Fertility, Heat Tolerance, Longevity, and Other. Pooled estimates of heritability for PIND traits ranged from 0.201 ± 0.05 (energy-corrected milk) to 0.377 ± 0.06 (protein content), while pooled estimates of heritability for RIND traits ranged from 0.032 ± 0.02 (incidence of lameness, incidence of milk fever) to 0.497 ± 0.05 (measures of body weight). Pooled estimates of genetic correlations ranged from -0.360 ± 0.25 (protein content vs. milk acetone concentration) to 0.535 ± 0.72 (measures of fat-to-protein ratio vs. milk acetone concentration). Additionally, out of 243 potential genetic correlations between PIND and RIND traits that could have been reported, only 40 had enough published estimates to implement the meta-analysis model. Our results confirmed that the interactions between PIND and RIND traits are complex, and all relationships should be evaluated when incorporating novel traits into selection indices. This study provides a valuable reference for breeders looking to incorporate RIND traits for Holstein cattle into selection indices.

Pervasive biases in GWAS using family history of Alzheimer’s disease as proxy phenotypes

AbstractBackgroundUsing family health history as proxy phenotype has become a common approach in genome‐wide association studies (GWAS) of Alzheimer’s disease (AD). This approach leverages large samples in population biobanks where most mid‐aged participants do not have any AD diagnosis. However, methodological issues in GWAS‐by‐proxy (GWAX) and quality of its association results have not been carefully investigated.MethodWe performed GWAX on parental AD history in UK Biobank (N = 48,031 proxy cases and 315,286 controls). We then applied GWAS‐by‐subtraction to obtain the non‐AD component underlying AD GWAX. We computed genetic correlations of AD case‐control GWAS, AD GWAX, and the non‐AD component underlying GWAX with a suite of complex traits. We also explored the impact of various quality control procedures and additional covariates in AD GWAX analysis.ResultAD GWAS and GWAX showed drastically different genetic correlations with several other complex traits especially cognitive abilities (Figure 1). AD GWAX had a surprising genetic correlation with higher education (rg = 0.167, p = 1.7e‐11) as opposed to the negative AD‐education correlation observed for GWAS (rg = ‐0.133, p = 2.4e‐5). The positive genetic correlation between AD and cognition is explained by the non‐AD component in AD GWAX (rg = 0.260 with education, p = 5.2e‐11). The non‐AD component in GWAX also showed correlations with lower risks of health outcomes such as coronary artery disease (rg = ‐0.136, p = 2.8e‐3) and diabetes (rg = ‐0.206, p = 2.8e‐3), indicating substantial survival bias in samples reporting parental AD history. Adjusting for parental age in GWAX substantially reduced but did not fully remove the genetic correlation of AD and higher education (rg = 0.013, p = 0.67), hinting at additional unaccounted factors in the current GWAX practice. We also provide evidence that genetic correlation between family health history awareness and education (rg = 0.285, p = 1.4e‐10) leads to these biases in GWAX associations.ConclusionGWAX based on parental health history introduces substantial and systematic biases in AD genetic associations due to the non‐representativeness of the biobank health history survey. Naively combining GWAX with regular case‐control GWAS will lead to misleading results both at the single variant level and in genome‐wide analyses such as genetic correlation estimation and polygenic risk score applications.

Genetic overlap between cortical brain morphometry and frontotemporal dementia risk

AbstractBackgroundFrontotemporal dementia (FTD) has a complex genetic aetiology, where the precise mechanisms underlying the selective vulnerability of brain regions remain unknown.MethodWe leveraged summary‐based data from genome‐wide association studies (GWASs) and performed LD‐score regression to estimate pairwise genetic correlations between FTD risk and cortical brain imaging. Then, we isolate specific genomic loci with a shared aetiology between FTD and brain structure. We also performed functional annotation, summary‐based‐data Mendelian randomisation for eQTL using human peripheral blood and brain tissue data and evaluated the gene expression in mice targeted brain regions to better understand the dynamics of the FTD candidate genes.ResultPairwise genetic correlation estimates between FTD and brain morphology measures were high but not statistically significant. We identified five brain regions with a strong genetic correlation (rg &gt; 0.45) with FTD risk. Functional annotation identified eight protein‐coding genes. Building upon these findings, we show in a mouse model of FTD that cortical NSF expression decreases with age.ConclusionOur results highlight the molecular and genetic overlap between brain morphology and higher risk for FTD, specifically for the right inferior parietal surface area and right medial orbitofrontal cortical thickness. In addition, our findings implicate NSF gene expression in the aetiology of FTD.

Genetics of sleep medication purchases suggests causality from sleep problems to psychiatric traits.

Over 10% of the population in Europe and in the United States use sleep medication to manage sleep problems. Our objective was to elucidate genetic risk factors and clinical correlates that contribute to sleep medication purchase and estimate the comorbid impact of sleep problems. We performed epidemiological analysis for psychiatric diagnoses, and genetic association studies of sleep medication purchase in 797 714 individuals from FinnGen Release 7 (N = 311 892) and from the UK Biobank (N = 485 822). Post-association analyses included genetic correlation, co-localization, Mendelian randomization (MR), and polygenic risk estimation. In a GWAS we identified 27 genetic loci significantly associated with sleep medication, located in genes associated with sleep; AUTS2, CACNA1C, MEIS1, KIRREL3, PAX8, GABRA2, psychiatric traits; CACNA1C, HIST1H2BD, NUDT12. TOPAZ1 and TSNARE1. Co-localization and expression analysis emphasized effects on the KPNA2, GABRA2, and CACNA1C expression in the brain. Sleep medications use was epidemiologically related to psychiatric traits in FinnGen (OR [95% (CI)] = 3.86 [3.78 to 3.94], p < 2 × 10-16), and the association was accentuated by genetic correlation and MR; depression (rg = 0.55 (0.027), p = 2.86 × 10-89, p MR = 4.5 × 10-5), schizophrenia (rg = 0.25 (0.026), p = 2.52 × 10-21, p MR = 2 × 10-4), and anxiety (rg = 0.44 (0.047), p = 2.88 × 10-27, p MR = 8.6 × 10-12). These results demonstrate the genetics behind sleep problems and the association between sleep problems and psychiatric traits. Our results highlight the scientific basis for sleep management in treating the impact of psychiatric diseases.