Linear Random Regression Models Research Articles

Genetic parameters for dry matter intake, energy balance, residual energy intake, and liability to diseases in German Holstein and Fleckvieh dairy cows.

Selection for feed efficiency (FE) is a hot topic in dairy cow breeding. Dry matter intake (DMI) and residual energy intake (REI) are mostly discussed as new selection traits. Selection for lower DMI or REI seems to increase FE if other traits, such as milk yield or health, are not affected negatively. However, genetic relationships with other traits have not been adequately investigated because of the difficulties in recording sufficient feed intake data for genetic evaluations. The aim of this study was to examine the genetic relationships between FE-related traits and liability to diseases throughout lactation. First, heritabilities for all traits are presented. Subsequently, genetic correlations between DMI, energy-corrected milk yield, energy balance (EB), and REI on the one hand and 3 disease categories (mastitis, claw and leg diseases, and all diseases) on the other throughout lactation in German Holstein (GH) dairy cows are illustrated. Production and health data from the projects optiKuh and eMissionCow were used. Data consisted of weekly observations recorded over a 325-wk period in 2,387 GH and over a 300-wk period in 632 Fleckvieh (FV) primiparous and multiparous dairy cows from 13 dairy research farms in Germany. Variance and covariance components were estimated univariately or bivariately with linear random regression models for production data and threshold random regression models for health data. Heritabilities for DMI, EB, and REI were on average 0.17 and 0.15, 0.14 and 0.15, as well as 0.11 and 0.14 in GH and FV, respectively. Heritabilities on the underlying scale for mastitis, claw and leg diseases, and all diseases were on average 0.17 and 0.16, 0.18 and 0.12, as well as 0.15 and 0.11 in GH and FV, respectively. In GH, almost all genetic correlations were negative, especially in early lactation. Within the first 50 d in milk, genetic correlations between DMI and REI on the one hand and disease categories on the other ranged from -0.25 to -0.14 for mastitis, from -0.31 to -0.13 for claw and leg diseases, and from -0.58 to -0.30 for all diseases. Consequently, selection for lower DMI or REI could lead to a higher liability to diseases, especially in early lactation. A possibility to mitigate these undesirable side effects could be lactation stage-specific selection for FE. For FV, further studies with more data are needed to assess genetic relationships.

Residual energy intake, energy balance, and liability to diseases: Genetic parameters and relationships in German Holstein dairy cows

Residual energy intake (REI) is an often-suggested trait for direct selection of dairy cows for feed efficiency. Cows with lower REI seem to be more efficient but are also in a more severe negative energy balance (EB), especially in early lactation. A negative EB leads to a higher liability to diseases. Due to this fact, this study aims to investigate the genetic relationship between REI and liability to diseases. Health and production data were recorded from 1,370 German Holstein dairy cows from 8 research farms over a period of 2 yr. We calculated 2 phenotypes for REI that considered the following energy sinks: milk energy content, metabolic body weight, body weight change, body condition score, and body condition score change. Genetic parameters were estimated with threshold or linear random regression models from days in milk (DIM) 1 to 305. Heritabilities for REI, EB, and all diseases ranged from 0.12 to 0.39, 0.15 to 0.31, and 0.09 to 0.20, respectively. Genetic correlations between selected DIM for REI and EB were higher for adjacent DIM than for more distant DIM. Pearson correlation coefficients between estimated breeding values (EBV) for REI and EB varied between 0.47 and 0.81; they were highest in mid lactation. Correlations between EBV for all diseases and REI as well as EB were negative, with lowest values in early lactation. Within the first 50 DIM, proportions of diseased days for cows with lowest EBV for REI were almost twice as high as for cows with highest EBV for REI. In conclusion, selecting dairy cows for lower REI should be treated with caution because of an unfavorable relationship with liability to diseases, especially in early lactation.

260 Genetic prediction for first-service conception rate in Angus heifers using a random regression model

Abstract First-service conception rate (FSCR) can be defined as the probability of a heifer conceiving in response to her first artificial insemination (AI). Given the binary nature of its phenotypes, FSCR has been typically evaluated using animal threshold models (ATM). However, susceptibility of these models to the extreme-category problem (ECP) limits their ability to use all available information to calculate Expected Progeny Differences (EPD). Random regression models (RRM) represent an alternative method to evaluate binary traits, and they are not affected by ECP. Nevertheless, RRM were originally developed to analyze longitudinal traits, so their usefulness to evaluate traits with singly observed phenotypes remains unclear. Therefore, objectives herein were to evaluate the feasibility of a RRM genetic prediction for heifer FSCR by comparing its resulting EPD and genetic parameters to those obtained with a traditional ATM. Breeding and ultrasound records of 4,334 Angus heifers (progeny of 354 sires and 1,626 dams) collected between 1992 to 2019 at the Colorado State University Beef Improvement Center were utilized. Observations for FSCR (1, successful; 0, unsuccessful) were defined by fetal age at pregnancy inspections performed approximately 130 d post-AI. Traditional FSCR evaluation was performed using a univariate BLUP threshold animal model, whereas an alternative evaluation was performed by regressing FSCR on age at AI using a linear RRM with Legendre Polynomials as the base function. Heritability estimates were 0.03 ± 0.02 for the ATM and 0.005 ± 0.001 for the average age at AI with the RRM, respectively. Pearson and rank correlations between EPD obtained with each method were 0.63 and 0.60, respectively. The regression coefficient of RRM predictions on those obtained with the ATM was 0.095. In conclusion, these results suggested that although a RRM genetic prediction for FSCR was feasible, a considerable degree of re-ranking occurred between the two methodologies.

Liability to diseases and their relation to dry matter intake and energy balance in German Holstein and Fleckvieh dairy cows

Dairy cow efficiency is increasingly important for future breeding decisions. The efficiency is determined mostly by dry matter intake (DMI). Reducing DMI seems to increase efficiency if milk yield remains the same, but resulting negative energy balance (EB) may cause health problems, especially in early lactation. Objectives of this study were to examine relationships between DMI and liability to diseases. Therefore, cow effects for DMI and EB were correlated with cow effects for 4 disease categories throughout lactation. Disease categories were mastitis, claw and leg diseases, metabolic diseases, and all diseases. In addition, this study presents relative percentages of diseased cows per days in milk (DIM), repeatability, and cow effect correlations for disease categories across DIM. A total of 1,370 German Holstein (GH) and 287 Fleckvieh (FV) primiparous and multiparous dairy cows from 12 dairy research farms in Germany were observed over a period of 2 yr. Farm staff and veterinarians recorded health data. We modeled health and production data with threshold random regression models and linear random regression models. From DIM 2 to 305 average daily DMI was 22.1 kg/d in GH and 20.2 kg/d in FV. Average weekly EB was 2.8 MJ of NEL/d in GH and 0.6 MJ of NEL/d in FV. Most diseases occurred in the first 20 DIM. Multiparous cows were more susceptible to diseases than primiparous cows. Relative percentages of diseased cows were highest for claw and leg diseases, followed by metabolic diseases and mastitis. Repeatability of disease categories and production traits was moderate to high. Cow effect correlations for disease categories were higher for adjacent lactation stages than for more distant lactation stages. Pearson correlation coefficients between cow effects for DMI, as well as EB, and disease categories were estimated from DIM 2 to 305. Almost all correlations were negative in GH, especially in early lactation. In FV, the course of correlations was similar to GH, but correlations were mostly more negative in early lactation. For the first 20 DIM, correlations ranged from -0.31 to 0.00 in GH and from -0.42 to -0.01 in FV. The results illustrate that future breeding for dairy cow efficiency should focus on DMI and EB in early lactation to avoid health problems.

TO002REDUCTION IN THE RATE OF EGFR DECLINE WITH SEMAGLUTIDE VS PLACEBO: A POST HOC POOLED ANALYSIS OF SUSTAIN 6 AND PIONEER 6

Abstract Background and Aims The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated that once-weekly (OW) subcutaneous (s.c.) semaglutide may have beneficial effects on kidney function. SUSTAIN 6 and the more recent PIONEER 6 CVOT (oral semaglutide) had similar designs and subject populations; both evaluated the effects of semaglutide compared with placebo on important macro- and microvascular outcomes. This post hoc analysis of pooled data from the two trials evaluated the effects of semaglutide vs placebo on kidney function, assessed by estimated glomerular filtration rate (eGFR) slope. Method Data for 6,480 subjects from SUSTAIN 6 (OW s.c. semaglutide 0.5 and 1.0 mg or placebo, n=3,297; median follow-up 2.1 years) and PIONEER 6 (oral semaglutide once-daily 14 mg or placebo, n=3,183; median follow-up 1.3 years) were pooled into two groups: semaglutide and placebo. Annual change in eGFR was compared between semaglutide and placebo in patients with eGFR data at baseline, both overall and by baseline eGFR subgroup (≥30–<60 or ≥60 mL/min/1.73 m2). Data were analysed using a linear random regression model with individual intercept and time slope. Estimated treatment difference (ETD) between annual rates of eGFR slope (from baseline to timepoint of interest) was calculated at Year 1 and Year 2 (Year 2 data predominantly from SUSTAIN 6); interaction p-values indicated differences between subgroups. Results In the overall treatment population, the annual rate of eGFR change was 0.60 mL/min/1.73 m2 (95% confidence interval [CI]: 0.31;0.90; p<0.0001) lower with semaglutide vs placebo in Year 1. In the subgroup with an eGFR ≥60 mL/min/1.73 m2 at baseline, the ETD for semaglutide vs placebo at Year 1 was 0.48 mL/min/1.73 m2/year (95% CI: 0.13;0.82). Whereas, at Year 1, the subgroup with eGFR ≥30–<60 mL/min/1.73 m2 had an ETD of 1.07 mL/min/1.73 m2/year (95% CI: 0.46;1.68) (Table). Accordingly, a numerically larger difference in ETD was observed in the eGFR ≥30–<60 mL/min/1.73 m2 vs the eGFR ≥60 mL/min/1.73 m2 subgroup (not statistically significant; pinteraction=0.21). Conclusion Semaglutide was associated with a significantly smaller decline in renal function compared with placebo in subjects across stages of impaired kidney function at baseline. Although benefits were observed in the overall population, the findings indicate that the primary benefit may be observed in those with established chronic kidney disease. Table Annual eGFR change with semaglutide or placebo and ETD between semaglutide and placebo in pooled SUSTAIN 6 and PIONEER 6 trials

Linking first lactation survival to milk yield and components and lactation persistency in Tunisian Holstein cows.

Genetic parameters were estimated for first lactation survival defined as a binary trait (alive or dead to second calving) and the curve shape traits of milk yield, fat and protein percentages using information from 25 981 primiparous Tunisian Holsteins. For each trait, shape curves (i.e. peak lactation, persistency), level of production adjusted to 305 days in milk (DIMs) for total milk yield (TMY), and average fat (TF %) and protein (TP %) percentages were defined. Variance components were estimated with a linear random regression model under three bivariate animal models. Production traits were modelled by fixed herd test-day (TD) interaction effects, fixed classes of 25 DIMs age of calving season of calving interaction effects, fixed classes of pregnancy, random environment effects and random additive genetic effects. Survival was modelled by fixed herd year of calving interaction effects and age of calving season of calving interaction effects, random permanent environment effects, and random additive genetic effects. Heritability () estimates were 0.03 () for survival and 0.23 (), 0.31 () and 0.31 () for TMY, TF % and TP %, respectively. Genetic correlations between survival and TMY, TF % and TP % were 0.26 (), () and (), respectively. Genetic correlations between survival and persistency for fat and protein percentages were () and (), respectively. Cows that had higher persistencies for fat and protein percentages were more likely not to survive.

Genetic parameters for stayability to consecutive calvings in Zebu cattle

Longer-lived cows tend to be more profitable and the stayability trait is a selection criterion correlated to longevity. An alternative to the traditional approach to evaluate stayability is its definition based on consecutive calvings, whose main advantage is the more accurate evaluation of young bulls. However, no study using this alternative approach has been conducted for Zebu breeds. Therefore, the objective of this study was to compare linear random regression models to fit stayability to consecutive calvings of Guzerá, Nelore and Tabapuã cows and to estimate genetic parameters for this trait in the respective breeds. Data up to the eighth calving were used. The models included the fixed effects of age at first calving and year-season of birth of the cow and the random effects of contemporary group, additive genetic, permanent environmental and residual. Random regressions were modeled by orthogonal Legendre polynomials of order 1 to 4 (2 to 5 coefficients) for contemporary group, additive genetic and permanent environmental effects. Using Deviance Information Criterion as the selection criterion, the model with 4 regression coefficients for each effect was the most adequate for the Nelore and Tabapuã breeds and the model with 5 coefficients is recommended for the Guzerá breed. For Guzerá, heritabilities ranged from 0.05 to 0.08, showing a quadratic trend with a peak between the fourth and sixth calving. For the Nelore and Tabapuã breeds, the estimates ranged from 0.03 to 0.07 and from 0.03 to 0.08, respectively, and increased with increasing calving number. The additive genetic correlations exhibited a similar trend among breeds and were higher for stayability between closer calvings. Even between more distant calvings (second v. eighth), stayability showed a moderate to high genetic correlation, which was 0.77, 0.57 and 0.79 for the Guzerá, Nelore and Tabapuã breeds, respectively. For Guzerá, when the models with 4 or 5 regression coefficients were compared, the rank correlations between predicted breeding values for the intercept were always higher than 0.99, indicating the possibility of practical application of the least parameterized model. In conclusion, the model with 4 random regression coefficients is recommended for the genetic evaluation of stayability to consecutive calvings in Zebu cattle.

Genetic component of sensitivity to heat stress for nonreturn rate of Brazilian Holstein cattle

The objectives of the present study were: 1) to investigate variation in the genetic component of heat stress for nonreturn rate at 56 days after first artificial insemination (NR56); 2) to identify and characterize the genotype by environment interaction (G × E) due to heat stress for NR56 of Brazilian Holstein cattle. A linear random regression model (reaction norm model) was applied to 51,748 NR56 records of 28,595 heifers and multiparous cows. The decline in NR56 due to heat stress was more pronounced in milking cows compared to heifers. The age of females at first artificial insemination and temperature-humidity index (THI) exerted an important influence on the genetic parameters of NR56. Several evidence of G × E on NR56 were found as the high slope/intercept ratio and frequent intersection of reaction norms. Additionally, the genetic correlation between NR56 at opposite extremes of the THI scale reached estimates below zero, indicating that few of the same genes are responsible for NR56 under conditions of thermoneutrality and heat stress. The genetic evaluation and selection for NR56 in Holstein cattle reared under (sub)tropical conditions should therefore take into consideration the genetic variation on age at insemination and G × E due to heat stress.

Metabolisable protein supply to lactating dairy cows increased with increasing dry matter concentration in grass-clover silage

The aim of this experiment was to study the effect of increased dry matter (DM) concentration in grass-clover silage, obtained by extending the pre-wilting period before ensiling, on the amount of metabolisable protein (MP) supplied to lactating dairy cows. Spring growth and first regrowth of grass-clover swards grown by two Danish organic farmers were cut and pre-wilted to a planned DM concentration of 350 and 700g/kg, respectively, giving in total eight silages with DM concentrations ranging from 283 to 725g/kg. Four Holstein dairy cows in late lactation with fistulae in rumen, duodenum and ileum were included in a crossover design, with five periods of 21 d. The cows were fed ad libitum with the experimental silages without any concentrate, but with daily supply of minerals and vitamins. Feed intake was registered daily and in the last week of each period 12 subsamples of duodenal and ileal chyme and faeces, respectively, were collected over 94h to cover the diurnal variation, pooled, and subsequently analysed. Rumen fluid was collected in same sampling procedure. To estimate the duodenal flow of microbial protein, microbes were isolated from the rumen and analysed for amino acids (AA) and purines. Methane (CH4) production was measured the last two days in each period in open-circuit respiration chambers. Results were analysed using a linear random regression model with DM concentration as fixed effect, cow and cut number x farmer as random intercepts and with a cut number x farmer random slope. The amount of AA digested in the small intestine increased (P=0.024) by 5.59g/kg DM intake with each increase in silage DM concentration of 100g/kg. The increased digestion of AA in the small intestine was caused by a higher small intestinal digestibility of AA and a tendency towards a higher duodenal flow of AA. The higher duodenal flow of AA derived from a lower rumen degradation of feed protein and a tendency towards a higher microbial synthesis in the rumen. Fibre digestibility and CH4 production were not affected by silage DM concentration. In conclusion, MP concentration in grass-clover silage can be improved by pre-wilting to a higher DM concentration before ensiling.

Automatic detection of lameness in gestating group-housed sows using positioning and acceleration measurements

Lameness is an important issue in group-housed sows. Automatic detection systems are a beneficial diagnostic tool to support management. The aim of the present study was to evaluate data of a positioning system including acceleration measurements to detect lameness in group-housed sows. Data were acquired at the Futterkamp research farm from May 2012 until April 2013. In the gestation unit, 212 group-housed sows were equipped with an ear sensor to sample position and acceleration per sow and second. Three activity indices were calculated per sow and day: path length walked by a sow during the day (Path), number of squares (25×25 cm) visited during the day (Square) and variance of the acceleration measurement during the day (Acc). In addition, data on lameness treatments of the sows and a weekly lameness score were used as reference systems. To determine the influence of a lameness event, all indices were analysed in a linear random regression model. Test day, parity class and day before treatment had a significant influence on all activity indices (P<0.05). In healthy sows, indices Path and Square increased with increasing parity, whereas variance slightly decreased. The indices Path and Square showed a decreasing trend in a 14-day period before a lameness treatment and to a smaller extent before a lameness score of 2 (severe lameness). For the index acceleration, there was no obvious difference between the lame and non-lame periods. In conclusion, positioning and acceleration measurements with ear sensors can be used to describe the activity pattern of sows. However, improvements in sampling rate and analysis techniques should be made for a practical application as an automatic lameness detection system.

Short communication: Genetic relationships between claw disorders, protein yield, and somatic cell score by days in milk

The aim of the present study was to infer daily genetic relationships between the selected claw disorders digital dermatitis, sole ulcer (SU), and interdigital hyperplasia (IH) and protein yield and the udder health indicator somatic cell score (SCS). Data were from 26,651 Holstein cows kept in 15 selected large-scale herds located in the region of Thuringia in the eastern part of Germany. Herds are characterized by organized data recording for novel health traits, and for the present study, claw disorders from the years 2008 to 2012 were used. A longitudinal and binary health data structure was created by assigning claw disorders to adjacent official test days. No entry of a claw disorder within a given interval of approximately 30 d implied a score of 0 (healthy), and otherwise, a score of 1 (diseased). Threshold random regression models (RRM) were applied to binary health data, and linear RRM to Gaussian-distributed protein yield and SCS. Genetic correlations between protein yield and SCS for identical days in milk (DIM) only revealed a tendency for genetic antagonisms between DIM 40 and DIM 180, with a maximal genetic correlation (rg) of 0.14 at DIM 100. With regard to protein yield and claw disorders, the largest and moderate values of rg (~0.30), indicating a genetic antagonism between productivity and claw health, were found when correlating protein yield from DIM 300 with SU from DIM 160. Especially for SU and protein yield, time-lagged relationships were more pronounced than genetic relationships from the same test days. Genetic correlations between IH and protein yield were favorable and negative from calving to DIM 300. Generally, on the genetic scale, we found heterogeneous associations between protein yield and claw disorders (i.e., different rg at identical test days for different claw disorders, and also an alteration of rg for identical traits at different DIM). The SCS measured at d 20, 160, and 300 was genetically positively correlated with SU over the whole trajectory of 365 d, indicating a common genetic background for claw and udder health. A maximal value of 0.36 was found for the rg between SCS from d 300 and SU early in lactation. Additionally, a recursive effect was observed (i.e., rg=0.26 between SCS from d 20 and SU from d 340). Genetic correlations between SCS and IH, and between SCS and digital dermatitis, were close to zero and partly negative during lactation. Results showed the feasibility of threshold RRM applications to binary claw health data, and a changing genetic background in the course of lactation. From a practical perspective, and with regard to the herds used in this study, continuation of breeding on productivity will have different effects on incidences of different claw disorders, with the highest susceptibility to SU.

Random regression models for genetic evaluation of clinical mastitis in dairy cattle

A genetic analysis of longitudinal binary clinical mastitis (CM) data recorded on about 90 000 first-lactation Swedish Holstein cows was carried out using linear random regression models (RRM). This method for genetic evaluation of CM has theoretical advantages compared to the method of linear cross-sectional models (CSM), which is currently being used. The aim of this study was to investigate the feasibility and suitability of estimating genetic parameters and predicting breeding values for CM with a linear sire RRM. For validation purposes, the estimates and predictions from the RRM were compared to those from linear sire longitudinal multivariate models (LMVM) and CSM. For each cow, the period from 10 days before to 241 days after calving was divided into four 1-week intervals followed by eight 4-week intervals. Within each interval, presence or absence of CM was scored as ‘1’ or ‘0’. The linear RRM used to explain the trajectory of CM over time included a set of explanatory variables plus a third-order Legendre polynomial function of time for the sire effect. The time-dependent heritabilities and genetic correlations from the chosen RRM corresponded fairly well with estimates obtained from the linear LMVM for the separate intervals. Some discrepancy between the two methods was observed, with the more unstable results being obtained from the linear LMVM. Both methods indicated clearly that CM was not genetically the same trait throughout lactation. The correlations between predicted sire breeding values from the RRM, summarized over different time periods, and from linear CSM were rather high. They were, however, less than unity (0.74 to 0.96), which indicated some re-ranking of sires. Sire curves based on the time-specific breeding values from the RRM illustrated differences in intercept and slope among the best and the worst sires. To conclude, a linear sire RRM seemed to work well for genetic evaluation purposes, but was sensitive for estimation of genetic parameters.

Genetic change of feed intake curves in growing pigs using non‐linear two‐stage genetic analysis and linear random regression models

SummaryLongitudinal data of daily feed intake from 5245 young boars were analysed in this study in order to improve feed efficiency by changing the feed intake curve. Individual logistic and linear‐segmented functions were fitted, based on daily data of feed intake per boar, recorded during a test period of 9 weeks. Heterogeneous variance was considered by means of the power‐of‐the‐mean variance model. The mean estimated day on test corresponding to maximum increment in feed intake varied from 71 to 81 days using logistic function, and the mean estimated day on test at which the feed intake plateau was reached varied from 45 to 48 days on test, using a linear‐segmented function. High differences in the individual variation pattern of feed intake were obtained. A mixed model was fitted to individual estimates of function parameters. The uncertainty in individual estimation was taken into account by incorporating the estimated asymptotic covariance matrices. Estimates of heritability for parameters characterizing feed intake at the beginning of the test period ranged from 0.03 to 0.30. Selection based on parameters of a logistic function, using absolute residual estimation of variance heterogeneity, reduced feed intake at the end of the test period by 0.2 kg/day, while feed intake at the beginning of the test was slightly modified. With increasing individual information on daily feed intake, the two‐stage method was recommended. If individual observations on daily feed intake are sparse, random regression models were preferred in order to change the feed intake curve for breeding purposes.

Cannabis use and anxiety in daily life: a naturalistic investigation in a non-clinical population

The study's objective was to investigate in a non-clinical population the association between cannabis use and anxiety in daily life using the Experience Sampling Method (ESM). Seventy-nine subjects with high or low levels of cannabis use were selected among a sample of 685 undergraduate university students. ESM was used to collect information on cannabis use and state-anxiety in daily life. DSM-IV diagnoses were assessed using a structured clinical interview. Statistical analyses were performed using multilevel linear random regression models. There was no significant association between the level of state anxiety and cannabis use in daily life. However, a diagnosis of agoraphobia was significantly associated with increased likelihood of cannabis use, independent of state anxiety and other confounding factors. No evidence was found for an anxiolytic or anxiogenic effect of cannabis in daily life. This finding does not support the hypothesis that subjects with high levels of anxiety use cannabis as a means of self-medication. The association between agoraphobia and cannabis use in daily life may be explained by anticipatory anxiety secondary to previous cannabis-induced panic-like symptoms.