Hyperketonemia GWAS and parity-dependent SNP associations in Holstein dairy cows intensively sampled for blood β-hydroxybutyrate concentration

2020 ◽  
Vol 52 (8) ◽  
pp. 347-357
Author(s):  
Ryan S. Pralle ◽  
Nichol E. Schultz ◽  
Heather M. White ◽  
Kent A. Weigel
Keyword(s):  
Dairy Cows ◽  
Metabolic Pathways ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
A Genome ◽  
Screening Protocol ◽  
Control Procedures ◽  
Nuclear Polymorphism

Hyperketonemia (HYK) is a metabolic disorder that affects early postpartum dairy cows; however, there has been limited success in identifying genomic variants contributing to HYK susceptibility. We conducted a genome-wide association study (GWAS) using HYK phenotypes based on an intensive screening protocol, interrogated genotype interactions with parity group (GWIS), and evaluated the enrichment of annotated metabolic pathways. Holstein cows were enrolled into the experiment after parturition, and blood samples were collected at four timepoints between 5 and 18 days postpartum. Concentration of blood β-hydroxybutyrate (BHB) was quantified cow-side via a handheld BHB meter. Cows were labeled as a HYK case when at least one blood sample had BHB ≥ 1.2 mmol/L, and all other cows were considered non-HYK controls. After quality control procedures, 1,710 cows and 58,699 genotypes were available for further analysis. The GWAS and GWIS were performed using the forward feature select linear mixed model method. There was evidence for an association between ARS-BFGL-NGS-91238 and HYK susceptibility, as well as parity-dependent associations to HYK for BovineHD0600024247 and BovineHD1400023753. Candidate genes annotated to these single nuclear polymorphism associations have been previously associated with obesity, diabetes, insulin resistance, and fatty liver in humans and rodent models. Enrichment analysis revealed focal adhesion and axon guidance as metabolic pathways contributing to HYK etiology, while genetic variation in pathways related to insulin secretion and sensitivity may affect HYK susceptibility in a parity-dependent matter. In conclusion, the present work proposes several novel marker associations and metabolic pathways contributing to genetic risk for HYK susceptibility.

Abstract P358: Discovery Loci and Generalization of Platelet Count Associations in the Hispanic Community Health Study: Study of Latinos (HCHS/SoL)

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Chani J Hodonsky ◽  
Ursula Schick ◽  
Jean Morrison ◽  
Cathy Laurie ◽  
John H Eckfeldt ◽  
...  
Keyword(s):  
Platelet Count ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Structural Integrity ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
The United States ◽  
Actin Binding ◽  
Health Study ◽  
A Genome

Background: The biology of platelets_anuclear megakaryocyte fragments required for clotting_is well defined, with abnormalities resulting in clotting disorders ranging from asymptomatic to severe. Although platelet count (PLT) is highly heritable (h 2 =0.57 in NHANES), genetic regulation of this trait remains incompletely characterized. In particular, Hispanic Latinos are a diverse population in which the genetic variability of PLT has not been analyzed. We aimed to 1) identify novel loci associated with PLT in participants of HCHS/SoL; and 2) determine if previously identified PLT loci generalize to the Hispanic Latino population. Methods: We performed a genome-wide association study of PLT in 12,491 participants of HCHS/SoL, which includes individuals with Dominican, Puerto Rican, Mexican, Cuban, South American, and Central American ancestral origins residing in the United States. Participants were genotyped on the Illumina SoL Omni2.5M array and imputed to the 1000 Genomes Phase I Reference panel. We implemented linear mixed-model regression assuming an additive genetic model, adjusting for sex, age, study center, ancestry and sample weights, and including random effects for individual relatedness, household, and block group. Results: Ten independent loci were significantly (α = 5x10 -8 ) associated with PLT in HCHS/SoL and 13 of 57 previously identified platelet-count GWAS loci generalized to HCHS/SoL (+/-500kb, α = 8.78x10 -4 ). Discovery loci included a significant association near GABBR1 (rs3131857, MAF = 40%, β = -0.16) and a suggestive association near ETV7 (rs9470264, MAF = 20%, β = -0.19). Furthermore, a noncoding variant in ACTN1 was associated with increased PLT (rs117672662, MAF = 6%, β = 0.61); ACTN1 codes for alpha-actinin, a multi-isoform actin-binding protein involved in cytoskeleton organization and platelet/megakaryocyte structural integrity. Missense mutations in ACTN1 were recently implicated in congenital thrombocytopenia; exome sequencing also associated this locus with PLT, which supports a potential functional role in PLT for this gene. Conditional regression analyses to assess secondary association signals are in progress. Conclusions: Genetic associations in two discovery loci ( ETV7 and GABBR1 ) underscore the benefit of using diverse populations in GWAS. Expanding the number of loci associated with platelet count will help elucidate disease mechanisms and develop approaches to treat platelet disorders in populations of all ancestries.

scholarly journals Genomic analysis of European bovine Staphylococcus aureus from clinical versus subclinical mastitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jurriaan Hoekstra ◽  
Aldert L. Zomer ◽  
Victor P. M. G. Rutten ◽  
Lindert Benedictus ◽  
Arjan Stegeman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Outcome ◽  
Virulence Genes ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Bovine Mastitis ◽  
Subclinical Mastitis ◽  
Clinical Severity ◽  
A Genome

Abstract Intramammary infections (IMI) with Staphylococcus aureus are a common cause of bovine mastitis and can result in both clinical (CM) or subclinical mastitis (SCM). Although bacterial isolates of S. aureus differ in their virulence potential it is largely unclear which bacterial virulence factors are responsible for increased clinical severity. We performed a genome wide association study and used a generalized linear mixed model to investigate the correlation between gene carriage, lineage and clinical outcome of IMI in a collection of S. aureus isolates from cattle with CM (n = 125) and SCM (n = 151) from 11 European countries. An additional aim was to describe the genetic variation of bovine S. aureus in Europa. The dominant lineages in our collection were clonal complex (CC) 151 (81/276, 29.3%), CC97 (54/276, 19.6%), CC479 (32/276, 11.6%) and CC398 (19/276, 6.9%). Virulence and antimicrobial resistance (AMR) gene carriage was highly associated with CC. Among a selection of nine virulence and AMR genes, CC151, CC479 and CC133 carried more virulence genes than other CCs, and CC398 was associated with AMR gene carriage. Whereas CC151, CC97 were widespread in Europe, CC479, CC398 and CC8 were only found in specific countries. Compared to CC151, CC479 was associated with CM rather than SCM (OR 3.62; 95% CI 1.38–9.50) and the other CCs were not. Multiple genes were associated with CM, but due to the clustering within CC of carriage of these genes, it was not possible to differentiate between the effect of gene carriage and CC on clinical outcome of IMI. Nevertheless, this study demonstrates that characterization of S. aureus CC and virulence genes helps to predict the likelihood of the occurrence of CM following S. aureus IMI and highlights the potential benefit of diagnostics tools to identify S. aureus CC during bovine mastitis.

scholarly journals Changes in Dairy Cow Behavior with and without Assistance at Calving

Agriculture ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 722
Author(s):  
Bethan Cavendish ◽  
John McDonagh ◽  
Georgios Tzimiropoulos ◽  
Kimberley R. Slinger ◽  
Zoë J. Huggett ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Video Surveillance ◽  
Dairy Cow ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Generalized Linear Mixed Model ◽  
Behavioral Data ◽  
Behavioral Patterns ◽  
Holstein Friesian ◽  
Time Periods

The aim of this study was to characterize calving behavior of dairy cows and to compare the duration and frequency of behaviors for assisted and unassisted dairy cows at calving. Behavioral data from nine hours prior to calving were collected for 35 Holstein-Friesian dairy cows. Cows were continuously monitored under 24 h video surveillance. The behaviors of standing, lying, walking, shuffle, eating, drinking and contractions were recorded for each cow until birth. A generalized linear mixed model was used to assess differences in the duration and frequency of behaviors prior to calving for assisted and unassisted cows. The nine hours prior to calving was assessed in three-hour time periods. The study found that the cows spent a large proportion of their time either lying (0.49) or standing (0.35), with a higher frequency of standing (0.36) and shuffle (0.26) bouts than other behaviors during the study. There were no differences in behavior between assisted and unassisted cows. During the three-hours prior to calving, the duration and bouts of lying, including contractions, were higher than during other time periods. While changes in behavior failed to identify an association with calving assistance, the monitoring of behavioral patterns could be used as an alert to the progress of parturition.

scholarly journals Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms

2020 ◽  
pp. annrheumdis-2020-218481 ◽  
Author(s):  
Elena López-Isac ◽  
Samantha L Smith ◽  
Miranda C Marion ◽  
Abigail Wood ◽  
Marc Sudman ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Fine Mapping ◽  
Target Genes ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Enrichment Analysis ◽  
Joint Analysis ◽  
Integrative Approach ◽  
Nucleotide Polymorphisms ◽  
A Genome

ObjectivesJuvenile idiopathic arthritis (JIA) is the most prevalent form of juvenile rheumatic disease. Our understanding of the genetic risk factors for this disease is limited due to low disease prevalence and extensive clinical heterogeneity. The objective of this research is to identify novel JIA susceptibility variants and link these variants to target genes, which is essential to facilitate the translation of genetic discoveries to clinical benefit.MethodsWe performed a genome-wide association study (GWAS) in 3305 patients and 9196 healthy controls, and used a Bayesian model selection approach to systematically investigate specificity and sharing of associated loci across JIA clinical subtypes. Suggestive signals were followed-up for meta-analysis with a previous GWAS (2751 cases/15 886 controls). We tested for enrichment of association signals in a broad range of functional annotations, and integrated statistical fine-mapping and experimental data to identify target genes.ResultsOur analysis provides evidence to support joint analysis of all JIA subtypes with the identification of five novel significant loci. Fine-mapping nominated causal single nucleotide polymorphisms with posterior inclusion probabilities ≥50% in five JIA loci. Enrichment analysis identified RELA and EBF1 as key transcription factors contributing to disease risk. Our integrative approach provided compelling evidence to prioritise target genes at six loci, highlighting mechanistic insights for the disease biology and IL6ST as a potential drug target.ConclusionsIn a large JIA GWAS, we identify five novel risk loci and describe potential function of JIA association signals that will be informative for future experimental works and therapeutic strategies.

scholarly journals Genome-Wide Association Study of Postoperative Cognitive Dysfunction in Older Surgical Patients

2020 ◽  
Author(s):  
Marc Rickenbacher ◽  
Céline S Reinbold ◽  
Stefan Herms ◽  
Per Hoffmann ◽  
Sven Cichon ◽  
...  
Keyword(s):  
Association Study ◽  
Candidate Genes ◽  
Cognitive Dysfunction ◽  
Genome Wide Association Study ◽  
Postoperative Cognitive Dysfunction ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

Abstract Background: Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication after surgery and anesthesia, particularly in elderly patients. Various studies have suggested genetic risk factors for POCD. The study aimed to detect genome-wide associations of POCD in older patients.Methods: In this prospective observational cohort study, participants aged ≥65 years completed a set of neuropsychological tests before, at 1 week, and 3 months after major noncardiac surgery. Test variables were converted into standard scores (z-scores) based on demographic characteristics. POCD was diagnosed if the decline was >1 standard deviation in ≥2 of the 15 variables in the assessment battery. A genome-wide association study (GWAS) was performed to determine potential alleles that are linked to the POCD phenotype. In addition, candidate genes for POCD were identified in a literature search for further analysis.Results: Sixty-three patients with blood samples were included in the study. POCD was diagnosed in 47.6% of patients at 1 week and in 34.2% of patients at 3 months after surgery. Insufficient sample quality led to exclusion of 26 patients. In the remaining 37 patients, a GWAS was performed, but no association (P < 5*10-8) with POCD was found. The subsequent gene set enrichment analysis of 34 candidate genes did not reveal any significant associations.Conclusion: In this patient cohort, a GWAS did not reveal an association between specific genetic alleles and POCD at 1 week and 3 months after surgery. Future genetic analysis should focus on specific candidate genes for POCD.Trial registration: ClinicalTrials.gov (NCT02864173)

scholarly journals Genome-wide association study reveals 14 new SNPs and confirms two structural variants highly associated with the horned/polled phenotype in goats

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiazhong Guo ◽  
Rui Jiang ◽  
Ayi Mao ◽  
George E. Liu ◽  
Siyuan Zhan ◽  
...  
Keyword(s):  
Association Study ◽  
Mixed Model ◽  
Genome Wide Association Study ◽  
Insertion Site ◽  
Genome Wide Association ◽  
Chromosome 1 ◽  
Structural Variants ◽  
Diagnostic Pcr ◽  
Genome Wide ◽  
A Genome

Abstract Background There is a long-term interest in investigating the genetic basis of the horned/polled phenotype in domestic goats. Here, we report a genome-wide association study (GWAS) to detect the genetic loci affecting the polled phenotype in goats. Results We obtained a total of 13,980,209 biallelic SNPs, using the genotyping-by-sequencing data from 45 Jintang Black (JT) goats, which included 32 female and nine male goats, and four individuals with the polled intersex syndrome (PIS). Using a mixed-model based GWAS, we identified two association signals, which were located at 150,334,857–150,817,260 bp (P = 5.15 × 10− 119) and 128,286,704–131,306,537 bp (P = 2.74 × 10− 15) on chromosome 1. The genotype distributions of the 14 most significantly associated SNPs were completely correlated with horn status in goats, based on the whole-genome sequencing (WGS) data from JT and two other Chinese horned breeds. However, variant annotation suggested that none of the detected SNPs within the associated regions were plausible causal mutations. Via additional read-depth analyses and visual inspections of WGS data, we found a 10.1-kb deletion (CHI1:g. 129424781_129434939del) and a 480-kb duplication (CHI1:150,334,286–150,818,098 bp) encompassing two genes KCNJ15 and ERG in the associated regions of polled and PIS-affected goats. Notably, the 10.1-kb deletion also served as the insertion site for the 480-kb duplication, as validated by PCR and Sanger sequencing. Our WGS genotyping showed that all horned goats were homozygous for the reference alleles without either the structural variants (SVs), whereas the PIS-affected goats were homozygous for both the SVs. We also demonstrated that horned, polled, and PIS-affected individuals among 333 goats from JT and three other Chinese horned breeds can be accurately classified via PCR amplification and agarose gel electrophoresis of two fragments in both SVs. Conclusion Our results revealed that two genomic regions on chromosome 1 are major loci affecting the polled phenotypes in goats. We provided a diagnostic PCR to accurately classify horned, polled, and PIS-affected goats, which will enable a reliable genetic test for the early-in-life prediction of horn status in goats.

scholarly journals Genetic and metabolic signatures of Salmonella enterica subsp. enterica associated with animal sources at the pangenomic scale

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Meryl Vila Nova ◽  
Kévin Durimel ◽  
Kévin La ◽  
Arnaud Felten ◽  
Philippe Bessières ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Public Health Issue ◽  
Nucleotide Polymorphisms ◽  
Genomic Signatures ◽  
Accessory Genes ◽  
European Nucleotide Archive ◽  
A Genome ◽  
Metabolic Signatures

Abstract Background Salmonella enterica subsp. enterica is a public health issue related to food safety, and its adaptation to animal sources remains poorly described at the pangenome scale. Firstly, serovars presenting potential mono- and multi-animal sources were selected from a curated and synthetized subset of Enterobase. The corresponding sequencing reads were downloaded from the European Nucleotide Archive (ENA) providing a balanced dataset of 440 Salmonella genomes in terms of serovars and sources (i). Secondly, the coregenome variants and accessory genes were detected (ii). Thirdly, single nucleotide polymorphisms and small insertions/deletions from the coregenome, as well as the accessory genes were associated to animal sources based on a microbial Genome Wide Association Study (GWAS) integrating an advanced correction of the population structure (iii). Lastly, a Gene Ontology Enrichment Analysis (GOEA) was applied to emphasize metabolic pathways mainly impacted by the pangenomic mutations associated to animal sources (iv). Results Based on a genome dataset including Salmonella serovars from mono- and multi-animal sources (i), 19,130 accessory genes and 178,351 coregenome variants were identified (ii). Among these pangenomic mutations, 52 genomic signatures (iii) and 9 over-enriched metabolic signatures (iv) were associated to avian, bovine, swine and fish sources by GWAS and GOEA, respectively. Conclusions Our results suggest that the genetic and metabolic determinants of Salmonella adaptation to animal sources may have been driven by the natural feeding environment of the animal, distinct livestock diets modified by human, environmental stimuli, physiological properties of the animal itself, and work habits for health protection of livestock.

Can post-milking insemination increase conception rate in high-producing Holstein cows under heat stress? A retrospective study

2019 ◽  
Vol 157 (03) ◽  
pp. 254-259
Author(s):  
R. Rahbar ◽  
A. Sadeghi-Sefidmazgi ◽  
R. Abdullahpour ◽  
A. Nejati-Javaremi
Keyword(s):  
Heat Stress ◽  
Dairy Cows ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Management Strategies ◽  
High Heat ◽  
Conception Rate ◽  
Low Fertility ◽  
Significant Interaction Effect ◽  
Dairy Animals

AbstractHeat stress, especially in countries with hot climates, is a major cause of low fertility in high-producing dairy herds. Management strategies are needed to help producers improve the reproductive performance of their dairy animals under such conditions. The current study aims to evaluate the effects of pre- and post-milking insemination on the conception rate (CR) in dairy cows. The dataset included 1294 insemination records leading to pregnancy in 708 lactating Holstein dairy cows. The GLIMMIX model procedure of SAS based on the generalized linear mixed model methodology was used to analyse the results of insemination (success or failure) as a binomial distribution with the logit link function. Differences were observed in CRs between pre- and post-milking insemination. The pregnancy odds ratio (OR) for post-milking insemination relative to that for pre-milking one was estimated at 1.90 [1.23‒2.91; 95% confidence interval (CI)]. Different levels of interaction were obtained between average daily milk production and time of insemination. In the high-producing group, the pregnancy OR for the post-milking relative to that for the pre-milking insemination was estimated at 3.53 (2.00‒6.24; 95% CI). A significant interaction effect was obtained between insemination time and the temperature-humidity index. A pregnancy OR of 2.52 (1.22‒4.14; 95% CI) was recorded for the cows inseminated after milking on days with higher levels of heat and humidity stress v. the pre-milking inseminated ones. Based on the results, post-milking insemination of high-producing cows increased CRs, especially on days with high heat and humidity stress.

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