Host Genetics of Response to Porcine Reproductive and Respiratory Syndrome in Sows: Antibody Response as an Indicator Trait for Improved Reproductive Performance

Antibody response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infection, measured as sample-to-positive (S/P) ratio, has been proposed as an indicator trait for improved reproductive performance during a PRRS outbreak in Landrace sows. However, this result has not yet been validated in Landrace sows or evaluated in terminal sire lines. The main objectives of this work were to validate the use of S/P ratio as an indicator trait to select pigs during a PRRS outbreak and to explore the genetic basis of antibody response to PRRSV. Farrowing data included 2,546 and 2,522 litters from 894 Duroc and 813 Landrace sows, respectively, split into pre-PRRS, PRRS, and post-PRRS phases. Blood samples were taken from 1,231 purebred sows (541 Landrace and 690 Duroc) following a PRRS outbreak for subsequent PRRSV ELISA analysis for S/P ratio measurement. All animals had high-density genotype data available (29,799 single nucleotide polymorphisms; SNPs). Genetic parameters and genome-wide association studies (GWAS) for S/P ratio were performed for each breed separately. Heritability estimates (± standard error) of S/P ratio during the PRRS outbreak were moderate, with 0.35 ± 0.08 for Duroc and 0.34 ± 0.09 for Landrace. During the PRRS outbreak, favorable genetic correlations of S/P ratio with the number of piglets born alive (0.61 ± 0.34), number of piglets born dead (−0.33 ± 0.32), and number of stillborn piglets (−0.27 ± 0.31) were observed for Landrace sows. For Duroc, the GWAS identified a major quantitative trait locus (QTL) on chromosome (Chr) 7 (24-15 megabases; Mb) explaining 15% of the total genetic variance accounted for by markers (TGVM), and another one on Chr 8 (25 Mb) explaining 2.4% of TGVM. For Landrace, QTL on Chr 7 (24–25 Mb) and Chr 7 (108–109 Mb), explaining 31% and 2.2% of TGVM, respectively, were identified. Some of the SNPs identified in these regions for S/P ratio were associated with reproductive performance but not during the PRRS outbreak. Genomic prediction accuracies for S/P ratio were moderate to high for the within-breed analysis. For the between-breed analysis, these were overall low. These results further support the use of S/P ratio as an indicator trait for improved reproductive performance during a PRRS outbreak in Landrace sows.

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27 Genomic relationship between antibody response to porcine reproductive and respiratory syndrome virus vaccination and reproductive performance in commercial sows

Journal of Animal Science ◽

10.1093/jas/skaa278.038 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 20-21

Author(s):

Leticia P Sanglard ◽

Rohan Fernando ◽

Kent A Gray ◽

Daniel C Linhares ◽

Jack C Dekkers ◽

...

Keyword(s):

Antibody Response ◽

Reproductive Performance ◽

Association Studies ◽

Genetic Correlations ◽

Reproductive Traits ◽

Respiratory Syndrome Virus ◽

Genome Wide Association Studies ◽

Prrs Virus ◽

Positive Ratio ◽

Commercial Farms

Abstract Antibody response, measured as sample-to-positive ratio (S/P), to porcine reproductive and respiratory syndrome (PRRS) after PRRS outbreaks has been proposed as an indicator trait to improve reproductive performance in PRRS-infected sows. However, waiting for a PRRS outbreak to occur and having different relationships in healthy pigs may limit the use of this trait. Thus, we proposed to investigate if this relationship also occurs between S/P to PRRS vaccination and reproductive performance in sows without exposure to PRRS. Nine hundred six F1 replacement gilts (139□17 days old) from two commercial farms were vaccinated with a commercial modified live PRRS virus vaccine. Blood samples were collected at 52 days after vaccination to measure S/P to PRRS and SNP genotyping. Reproductive performance included: number born alive (NBA), number of piglets weaned, number born mummified (MUM), number stillborn (NSB), and pre-weaning mortality (PWM) at parities (P) 1 to 3. Average performance was calculated for each trait per sow per year (PSY). Farrowing rate and age at first service were also analyzed. BayesC0 was used to estimate genetic correlations between S/P and reproductive performance. Bivariate genome-wide association studies of antibody response and reproductive traits were performed using BayesB. High genetic correlations between S/P and farrowing performance were identified for NBA_P1 (0.61±0.16), PWM_P2 (-0.64±0.15), PWM_P2 (-0.63±0.20), NSB_P3 (-0.84±0.05), MUM_P3 (-0.83±0.11), and NSB_PSY (-0.90±0.05). A QTL was identified on chromosome 7 (MHC region) for these reproductive traits and for S/P, explaining from 1.2% (PWM_P2) to 22.4% (S/P) of the genetic variance. SNP H3GA0020505 explained most of the variance in this region for these traits. Heterozygote animals for this SNP had overall better performance: greater S/P (P = 0.001), greater (P = 0.06) NBA_P1, and lesser (P = 0.06) MUM_P3 than other genotypes. These results suggest that antibody response to PRRS vaccination may be used as a genetic indicator to improve reproductive performance in commercial pigs.

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129 Genomic Relationship Between PRRSV Wild-type Infection and PRRSV Vaccination for Antibody Response and Reproductive Performance

Journal of Animal Science ◽

10.1093/jas/skab054.032 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 18-18

Author(s):

Leticia P Sanglard ◽

Felipe Hickmann ◽

Yijian Huang ◽

Kent A Gray ◽

Daniel Linhares ◽

...

Keyword(s):

Antibody Response ◽

Reproductive Performance ◽

Genetic Correlations ◽

Clinical Signs ◽

Respiratory Syndrome Virus ◽

Wild Type ◽

Large White ◽

Selection For ◽

Indicator Trait ◽

Type Infection

Abstract Immunoglobulin G antibody response, measured as sample-to-positive (S/P) ratio, to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) has been proposed as an indicator trait for improved reproductive performance in PRRSV-infected purebred sows and PRRSV-vaccinated crossbred gilts. In this study, we investigated the genetic correlations (rg) of S/P ratio following a PRRSV outbreak and PRRSV-vaccination with performance in non-exposed and PRRSV-exposed sows. PRRSV outbreak phase was defined based on previously described methodologies after the detection of typical clinical signs of PRRSV infection. 541 Landrace sows had S/P ratio measured at ~54 days after the beginning of the PRRSV outbreak (S/Poutbreak), and 906 Landrace x Large White naïve F1 gilts had S/P ratio measured at ~50 days after vaccination with a commercial modified live PRRSV vaccine (S/PVx). 711 and 428 Landrace sows had reproductive performance recorded before and during the PRRSV outbreak, respectively. 811 vaccinated F1 animals had farrowing performance for up to 3 parities. All animals were genotyped for ~28K SNPs. The estimate of rg of S/Poutbreakwith S/PVx was high (rg±SE = 0.72±0.18). Estimates of rg of S/Poutbreak with reproductive performance in F1 sows were low to moderate, ranging from 0.05±0.23 (number stillborn) to 0.30±0.20 (total number born). Estimates of rg of S/PVxwith reproductive performance in non-infected purebred sows were moderate and favorable with number born alive (0.50±0.23), but low (0 to -0.11±0.23) with litter mortality traits. Estimates of rg of S/PVx were moderate and negative (-0.47±0.18) with the number of mummies in PRRSV-infected purebred sows and low with other traits (-0.29±0.18 for total number born to 0.05±0.18 for number stillborn). These results indicate that selection for antibody response following a PRRSV outbreak collected in purebred sows and to PRRSV vaccination collected in commercial crossbred gilts may increase litter size of non-infected and PRRSV-exposed purebred and commercial crossbred sows.

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Association of CNVs with methylation variation

npj Genomic Medicine ◽

10.1038/s41525-020-00145-w ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Xinghua Shi ◽

Saranya Radhakrishnan ◽

Jia Wen ◽

Jin Yun Chen ◽

Junjie Chen ◽

...

Keyword(s):

Association Studies ◽

Copy Number Variants ◽

Cpg Methylation ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Cellular Phenotype ◽

Genome Wide ◽

A Genome ◽

Physical Interactions ◽

Trait Locus

Abstract Germline copy number variants (CNVs) and single-nucleotide polymorphisms (SNPs) form the basis of inter-individual genetic variation. Although the phenotypic effects of SNPs have been extensively investigated, the effects of CNVs is relatively less understood. To better characterize mechanisms by which CNVs affect cellular phenotype, we tested their association with variable CpG methylation in a genome-wide manner. Using paired CNV and methylation data from the 1000 genomes and HapMap projects, we identified genome-wide associations by methylation quantitative trait locus (mQTL) analysis. We found individual CNVs being associated with methylation of multiple CpGs and vice versa. CNV-associated methylation changes were correlated with gene expression. CNV-mQTLs were enriched for regulatory regions, transcription factor-binding sites (TFBSs), and were involved in long-range physical interactions with associated CpGs. Some CNV-mQTLs were associated with methylation of imprinted genes. Several CNV-mQTLs and/or associated genes were among those previously reported by genome-wide association studies (GWASs). We demonstrate that germline CNVs in the genome are associated with CpG methylation. Our findings suggest that structural variation together with methylation may affect cellular phenotype.

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Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB

Human Molecular Genetics ◽

10.1093/hmg/ddaa026 ◽

2020 ◽

Vol 29 (10) ◽

pp. 1581-1591 ◽

Cited By ~ 1

Author(s):

Mesude Bicak ◽

Xing Wang ◽

Xiaoni Gao ◽

Xing Xu ◽

Riina-Minna Väänänen ◽

...

Keyword(s):

Association Studies ◽

Meta Analysis ◽

Prostate Cancer Risk ◽

Fold Increase ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Normal Prostate ◽

Cis Acting ◽

Genome Wide ◽

Trait Locus

Abstract How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.

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Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

Psychological Medicine ◽

10.1017/s003329172100266x ◽

2021 ◽

pp. 1-9

Author(s):

Emma C. Johnson ◽

Manav Kapoor ◽

Alexander S. Hatoum ◽

Hang Zhou ◽

Renato Polimanti ◽

...

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Large Scale ◽

Association Studies ◽

Genetic Correlations ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genetic Covariance ◽

Specific Effects ◽

Genome Wide

Abstract Background Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. Methods We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. Results We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). Conclusions Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

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A Novel QTL and a Candidate Gene Are Associated with the Progressive Motility of Franches-Montagnes Stallion Spermatozoa after Thaw

Genes ◽

10.3390/genes12101501 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1501

Author(s):

Annik Imogen Gmel ◽

Dominik Burger ◽

Markus Neuditschko

Keyword(s):

Sperm Count ◽

Association Studies ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Progressive Motility ◽

Genome Wide ◽

Trait Locus ◽

Fertility Traits ◽

Substantial Drop

The use of frozen-thawed semen is an important reproduction tool to preserve the biodiversity of small, native horse breeds such as the Franches-Montagnes (FM). However, not all stallions produce cryotolerant semen with a progressive motility after thaw ≥ 35%. To improve our understanding of the genetic background of male fertility traits in both fresh and frozen-thawed semen, we performed genome-wide association studies (GWAS) on gel-free volume, sperm cell concentration, total sperm count, and progressive motility in fresh and frozen-thawed semen from 109 FM stallions using 335,494 genome-wide single nucleotide polymorphisms (SNPs). We identified one significant (p < 1.69 × 10−7) quantitative trait locus (QTL) on ECA6 within the SCN8A gene for progressive motility after thaw, which was previously associated with progressive motility in boars. Homozygous stallions showed a substantial drop in progressive motility after thaw. This QTL could be used to identify cryointolerant stallions, avoiding the costly cryopreservation process. Further studies are needed to confirm whether this QTL is also present in other horse breeds.

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127 Antibody Response as an Indicator Trait for Improved Reproductive Performance During a PRRSV Outbreak: Genetic Correlations of S/P Ratio with Reproductive Traits in Landrace and Duroc Sows

Journal of Animal Science ◽

10.1093/jas/skab054.034 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 19-20

Author(s):

Felipe Hickmann ◽

José Braccini Neto ◽

Luke M Kramer ◽

Kent A Gray ◽

Yijian Huang ◽

...

Keyword(s):

Antibody Response ◽

Reproductive Performance ◽

Genetic Correlations ◽

Reproductive Traits ◽

Respiratory Syndrome Virus ◽

Potential Indicator ◽

Host Genetic ◽

Heritability Estimates ◽

Terminal Sire ◽

Indicator Trait

Abstract Previous studies proposed the use of antibody response to Porcine Reproductive and Respiratory Syndrome virus (PRRSV), measured as sample-to-positive (S/P) ratio, as a potential indicator trait to improve the reproductive performance of PRRSV-infected Landrace sows. However, this indicator trait has not yet been validated in Landrace sows or evaluated in a terminal sire line, such as Duroc. The main objective of this work was to perform host-genetic analyses of S/P ratio and reproductive traits during a PRRSV outbreak in maternal and terminal breeds. The data consisted of 690 Duroc and 541 Landrace multiparous sows (1.9±1.2 and 2.3±1.5, respectively) with S/P ratio collected at approximately 54 days after the predicted beginning of the outbreak. Of these, 644 Duroc and 528 Landrace sows also had reproductive data recorded during the PRRSV outbreak comprising number of piglets born alive (NBA), stillborn piglets (NSB), mummified piglets (NBM), number born dead (NBD; sum of NSB and NBM), total number born (TNB; sum of NBA and NBD), and number weaned (NW). All animals had genotype data on ~30K SNPs common across both breeds. Heritability estimates (± standard error) of S/P ratio during the PRRSV outbreak were moderate, with 0.33±0.06 for Duroc and 0.28±0.07 for Landrace. Reproductive traits during the PRRSV outbreak had overall low heritability estimates (≤0.18). Favorable genetic correlations of S/P ratio with NBA (0.65±0.33), in accordance with previous studies, and NBD (-0.33±0.28) were observed for Landrace sows only. Estimates of genetic correlation with other traits were -0.21±0.30 (NBM), -0.12±0.29 (NSB), 0.10±0.38 (NW), and 0.54±1.29 (TNB) for Landrace. For Duroc, these estimates were weaker: -0.33±0.40 (NBA), 0.26±0.27 (NBA), and 0.28±0.30 (NW), with convergence issues for mortality traits. These results further support the use of S/P ratio as an indicator trait for improved reproductive performance during a PRRSV outbreak in Landrace sows.

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Causal Association between Periodontitis and Parkinson’s Disease: A Bidirectional Mendelian Randomization Study

Genes ◽

10.3390/genes12050772 ◽

2021 ◽

Vol 12 (5) ◽

pp. 772

Author(s):

João Botelho ◽

Vanessa Machado ◽

José João Mendes ◽

Paulo Mascarenhas

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Instrumental Variables ◽

Mendelian Randomization ◽

Association Studies ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genetic Liability ◽

Bidirectional Association

The latest evidence revealed a possible association between periodontitis and Parkinson’s disease (PD). We explored the causal relationship of this bidirectional association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on periodontitis and PD. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and eight non-overlapping SNPs of periodontitis from an additional GWAS for validation purposes. Instrumental variables to explore for the reverse causation included forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B = −0.0003, Standard Error [SE] 0.0003, p = 0.26). The eight independent SNPs (B = −0.0000, SE 0.0001, p = 0.99) validated this outcome. We also found no association of genetically primed PD towards periodontitis (B = −0.0001, SE 0.0001, p = 0.19). These MR study findings do not support a bidirectional causal genetic liability between periodontitis and PD. Further GWAS studies are needed to confirm the consistency of these results.

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Pharmacogenomics of Lithium Response in Bipolar Disorder

Pharmaceuticals ◽

10.3390/ph14040287 ◽

2021 ◽

Vol 14 (4) ◽

pp. 287

Author(s):

Courtney M. Vecera ◽

Gabriel R. Fries ◽

Lokesh R. Shahani ◽

Jair C. Soares ◽

Rodrigo Machado-Vieira

Keyword(s):

Bipolar Disorder ◽

Association Studies ◽

Mood Stabilizer ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Non Coding Rna ◽

Genome Wide ◽

Lithium Response ◽

Genetic Loading ◽

Long Non Coding Rna

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

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Investigation of gene–environment interactions in relation to tic severity

Journal of Neural Transmission ◽

10.1007/s00702-021-02396-y ◽

2021 ◽

Author(s):

Mohamed Abdulkadir ◽

Dongmei Yu ◽

Lisa Osiecki ◽

Robert A. King ◽

Thomas V. Fernandez ◽

...

Keyword(s):

Tourette Syndrome ◽

Association Studies ◽

Autism Spectrum ◽

Environment Interaction ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Linear Regression Models ◽

Compulsive Disorder ◽

Gene Environment ◽

Tic Severity

AbstractTourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

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