PSIV-16 Genome-wide association study of Rambouillet rams with angular limb deformities

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 301-302
Author(s):  
Gabrielle M Becker ◽  
Morgan R Stegemiller ◽  
Christopher S S Schauer ◽  
Whit C C Stewart ◽  
Brenda M Murdoch
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Principal Component ◽  
Genome Wide Association ◽  
P Value ◽  
Genetic Associations ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Limb Deformities

Abstract Lameness and limb deformities can be detrimental to range and breeding sheep. Growing animals are at an increased risk of angular limb deformities (ALD) and lameness, which adversely affects their mobility, breeding soundness and ultimately longevity. Ram testing allows developing ram lambs from different farms to be evaluated together under a consistent nutritive and environment management system. The aim of this study is to investigate rams from four ram test cohorts (North Dakota State University and University of Wyoming in two consecutive years) for genetic associations with ALD occurrence. In total 131 Rambouillet rams, including 17 ALD-affected and 114 unaffected, were genotyped using AxiomTM Ovine Genotyping Array (50K). A genome-wide association study was conducted using a recessive chi-square model with correction by principal component analysis (eigenstrat). A marker on chromosome eight is significantly (unadjusted P-value= 1.74e-08) associated with the incidence of ALD. This marker is located within the gene; branched chain keto acid dehydrogenase E1 subunit beta (BCKDHB). BCKDHB is associated with mitochondrial membranes and metabolism which is required for effective bone (osteoblast and chondrocytes) formation. It is proposed that altered branched amino acid metabolism in rapidly growing sheep with this genotype may impart risk of limb deformities classified as ALD. Identifying genetic associations with ALD in sheep may help detect animals with a higher propensity for ALD, which would provide producers with additional tools to make informed management and breeding decisions.

scholarly journals Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112,117)

2017 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
Gail Davies ◽  
David M. Howard ◽  
Lynsey S. Hall ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Hdl Cholesterol ◽  
Genome Wide Association ◽  
P Value ◽  
Uk Biobank ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Overlap

AbstractAlcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well known genetic variants in alcohol metabolizing genes, e.g. ALDH2, ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 8 independent loci. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, PXDN, CADM2 and TNFRSF11A. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (CRHR1, DRD2), and genes previously associated with alcohol consumption (AUTS2). GCTA-GREML analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (S.E.=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation between male and female alcohol consumption was 0.73 (S.E.=0.09, p-value = 1.37 x 10−16). Using LD score regression, genetic overlap was found between alcohol consumption and schizophrenia (rG=0.13, S.E=0.04), HDL cholesterol (rG=0.21, S.E=0.05), smoking (rG=0.49, S.E=0.06) and various anthropometric traits (e.g. Overweight, rG=-0.19, S.E.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies 4 novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

scholarly journals Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population

2021 ◽  
Vol 118 (11) ◽  
pp. e2004199118
Author(s):  
Marina Penova ◽  
Shuji Kawaguchi ◽  
Jun-ichirou Yasunaga ◽  
Takahisa Kawaguchi ◽  
Tomoo Sato ◽  
...  
Keyword(s):  
Amino Acid ◽  
Association Study ◽  
Proviral Load ◽  
Odds Ratio ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

HTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10−9) and class II (P = 1.21 × 10−8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10−5), HLA-B*07:02 (P = 4.97 × 10−10), HLA-DRB1*01:01 (P = 1.15 × 10−9) and HLA-DQB1*05:01 (P = 2.30 × 10−9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10−5), HLA-DRB1*15:01 (P = 1.06 × 10−5) and HLA-DQB1*06:02 (P = 1.78 × 10−6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10−10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.

Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
B. P. Schneider ◽  
L. Li ◽  
K. Miller ◽  
D. Flockhart ◽  
M. Radovich ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genetic Associations ◽  
Genome Wide ◽  
A Genome

scholarly journals The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response

2015 ◽  
Vol 5 (4) ◽  
pp. e553-e553 ◽  
Author(s):  
J M Biernacka ◽  
K Sangkuhl ◽  
G Jenkins ◽  
R M Whaley ◽  
P Barman ◽  
...  
Keyword(s):  
Association Study ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Genome Wide Association Study ◽  
Transmembrane Domain ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Research Network ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Abstract Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P=5.03E−08) and SNPs 5’ upstream of the neuregulin-1 gene, NRG1 (P=1.20E−06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.

A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14

2016 ◽  
Vol 76 (1) ◽  
pp. 310-314 ◽  
Author(s):  
Félicie Costantino ◽  
Alice Talpin ◽  
Roula Said-Nahal ◽  
Ariane Leboime ◽  
Elena Zinovieva ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Gwas Study ◽  
Genome Wide ◽  
Multiplex Families ◽  
Family Based

ObjectiveMore than 40 loci have been associated with ankylosing spondylitis (AS), but less is known about genetic associations in spondyloarthritis (SpA) as a whole. We conducted a family-based genome-wide association study (GWAS) to identify new non-major histocompatibility complex (MHC) genetic factors associated with SpA.Methods906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays. Association was tested with Unphased. The best-associated non-MHC single nucleotide polymorphisms (SNPs) were then genotyped in two independent familial cohorts (including 215 French and 294 North American patients with SpA, respectively) to replicate associations.Results43 non-MHC SNPs yielded an association signal with SpA in the discovery cohort (p<1×10−4). In the extension studies, association was replicated at a nominal p value of p<0.05 for 16 SNPs in the second cohort and for three SNPs in the third cohort. Combined analysis identified an association close to genome-wide significance between rs7761118, an intronic SNP of MAPK14, and SpA (p=3.5×10−7). Such association appeared to be independent of HLA-B27.ConclusionsWe report here for the first time a family-based GWAS study on SpA and identified an associated polymorphism near MAPK14. Further analyses are needed to better understand the functional basis of this genetic association.

scholarly journals Genetics of fasting and postprandial metabolite levels are overlapping

2018 ◽  
Vol 50 (4) ◽  
pp. 235-236
Author(s):  
Ruifang Li-Gao ◽  
Renée de Mutsert ◽  
Frits R. Rosendaal ◽  
Ko Willems van Dijk ◽  
Dennis O. Mook-Kanamori
Keyword(s):  
Association Study ◽  
Human Body ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genetic Associations ◽  
Mixed Meal ◽  
Genome Wide ◽  
A Genome ◽  
Metabolite Concentrations

In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the Biocrates AbsoluteIDQ p150 kit. However, the human body resides in a nonfasting state for the greater part of the day, and the genetic basis of postprandial metabolite concentrations remains largely unknown. We systematically examined these previously identified genetic associations in postprandial metabolite concentrations after a mixed meal. Of these 85 metabolites, 23 were identified with significant changes after the meal, for which 38 gene-metabolite associations were analyzed. Of these 38 associations, 31 gene-metabolite associations were replicated with postprandial metabolite concentrations. These data indicate that the genetics of fasting and postprandial metabolite levels are significantly overlapping.

scholarly journals Correction: Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130109 ◽  
Author(s):  
Giuseppe Matullo ◽  
Simonetta Guarrera ◽  
Marta Betti ◽  
Giovanni Fiorito ◽  
Daniela Ferrante ◽  
...  
Keyword(s):  
Association Study ◽  
Malignant Pleural Mesothelioma ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Pleural Mesothelioma ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

scholarly journals A Genome-Wide Association Study for Melatonin Secretion

2021 ◽  
Author(s):  
Pi-Hua Liu ◽  
Gwo-Tsann Chuang ◽  
Chia-Ni Hsiung ◽  
Wei-Shun Yang ◽  
Hsiao-Chia Ku ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
P Value ◽  
Melatonin Level ◽  
Nucleotide Polymorphisms ◽  
Melatonin Secretion ◽  
Genome Wide ◽  
A Genome ◽  
Wide Range

Abstract SummaryPurpose: Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). Methods: We initially enrolled 5,000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). Results: A total of 2,504 participants underwent the genome-wide analysis. Six candidate loci associated with log UMCR (P value ranging from 7.54 x 10-7 to 4.65 x 10-6) encompassing GALNT15, ZFHX3, NKAIN2, MME and NBPF22P were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with central nervous system function and clinical condition such as Alzheimer's disease or sleep disorders.Conclusions: We conducted the first GWAS for melatonin secretion and identified six candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

scholarly journals A Genome Wide Association Study Reveals Genetic Predisposition for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma By Variation in the PREP1-Cbs Locus

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2057-2057
Author(s):  
Florence Magrangeas ◽  
Rowan Kuiper ◽  
Hervé Avet-loiseau ◽  
Wilfried Gouraud ◽  
Catherine Guérin ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Association Study ◽  
Genetic Predisposition ◽  
Research Funding ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
P Value ◽  
Discovery Cohort ◽  
Genome Wide ◽  
A Genome

Abstract Introduction: Bortezomib has become an important part of myeloma therapy, despite the occurrence of toxicities such as bortezomib induced peripheral neuropathy (BiPN). Since effective prophylactic treatment is lacking, onset of BiPN can only be remedied by dose reduction or stop of treatment. Here, using a genome-wide genotyping method, we investigated the potential genetic predisposition to BiPN in MM patients who received bortezomib-dexamethasone (VD) induction therapy prior to autologous stem-cell transplantation (ASCT). Methods: We performed a genome-wide association study using the Affymetrix SNP 6.0 platform. In total 469 cases from the IFM 2005-01, IFM2007-02 clinical trials or routine diagnostic were included as discovery cohort. Another 114 samples from the HOVON-65/GMMG-HD4 trial were used as validation. Patients with BiPN grade 2 or higher after initiation of bortezomib treatment were assigned as cases (n=155 in discovery, n=40 in validation) and the remaining patients that did not developed BiPN were considered controls (n=314 in discovery, n=74 in validation). Additional exclusion criteria were a minor allele frequency ≤ 5%, genotype frequency < 95% or Hardy Weinberg equilibrium p-value <1 x 10-5; 371,075 tagging SNPs were thus included for analysis. Association of SNPs to BiPN was tested using a Cochran-Armitage trend test. Six SNPs were found with parametric p-value < 1 x 10-5. These SNPs were validated using the validation cohort. Results: Of three loci identified by six SNPs in the discovery cohort, one previously unreported gene locus (rs2839629) remained associated to BiPN in the validation data set. This locus at 21q22.3 had odd ratios of 1.89 (p<1x10-6) and 2.02 (p = 0.02) in the discovery and validation cohorts, respectively. It is localized in the 3’ UTR of PBX/knotted 1 homeobox 1 (PKNOX1; alias PREP1), which encodes for a homeodomain transcription factor. Amongst others, PKNOX1 may modulate levels of chemokine monocyte chemoattractant protein-1 (MCP-1). MCP-1 is universally increased in different models of peripheral neuropathic pain and may be considered as a biomarker of chronic pain (Zhang and de Koninck, J. Neurochem. 97:772-783 (2006)). Haplotype analysis revealed a strong linkage disequilibrium (LD, r2 = 0.87) to the neighbouring gene CBS which encodes an endogenous H2S-producing enzyme. The CBS-H2S signalling pathway is implicated in the pathogenesis of a variety of neurodegenerative and inflammatory disorders, and specifically in neuropathy models (Takahashi et al., Pain, 150, 183-191, 2010). Conclusions: Our data provides evidence for susceptibility to BiPN in MM by variation in the PREP1-CBS locus, and suggests a new potential target in neuro-protective strategies of treatment. Validation of this finding may allow for the identification of patients at increased risk of BiPN which may benefit alternative treatments such as carfilzomib and better clinical management of this toxicity. Disclosures Sonneveld: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Millenium: Honoraria, Research Funding. Moreau:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees.

A genome-wide association study in progressive multiple sclerosis

2012 ◽  
Vol 18 (10) ◽  
pp. 1384-1394 ◽  
Author(s):  
Filippo Martinelli-Boneschi ◽  
Federica Esposito ◽  
Paola Brambilla ◽  
Eva Lindström ◽  
Giovanni Lavorgna ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Axonal Guidance ◽  
Genome Wide Association ◽  
P Value ◽  
Suggestive Evidence ◽  
Genome Wide ◽  
A Genome ◽  
Herv Element

Background: The role played by genetic factors in influencing the clinical course of multiple sclerosis (MS) is not yet well established. Objective: We aimed to identify genetic variants associated with progressive MS (PrMS). Methods: We conducted a genome-wide association study (GWAS) in 197 patients with PrMS and 234 controls of Italian origin. We tested the top 20 single nucleotide polymorphisms (SNPs) with suggestive evidence of association ( p-value<10−4) in two independent sets of primary progressive MS cases and controls. Results: We identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD) with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934T, pcombined=6.7×10-16, OR=2.34, 95% CI=1.90–2.87), and a novel locus on chromosome 7q35 with suggestive evidence of association (rs996343G, pcombined=2.4×10-5, OR=0.70, 95% CI=0.59–0.83) which maps within a human endogenous retroviral (HERV) element. The new locus did not have a ‘ cis’ effect on RNA expression in lymphoblastic cell lines, but pathway analyses of ‘ trans’ effects point to an expression regulation of genes involved in neurodegeneration, including glutamate metabolism ( p<0.01) and axonal guidance signalling ( p<0.02). Conclusions: We have confirmed the established association with the HLA region and, despite the low statistical power of the study, we found suggestive evidence for association with a novel locus on chromosome 7, with a putative regulatory role.

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