PSI-18 Identifying genetic variants associated with grazing, walking, and slope use of cattle experiencing mild heat load

Abstract Rangeland is a valuable resource that can allow producers to cost effectively provide nutrients for grazing cattle. However, grazing behavior of cattle is adversely affected when the temperature humidity index is greater than 72. It is possible to select cattle that exhibit efficient grazing behavior even under mild heat stress. This study evaluated genetic associations with grazing behavior to help producers identify cows that will effectively use their rangeland pastures. Using genome-wide associations, this study identified single nucleotide polymorphisms (SNPs) associated with grazing time, walking time and max slope that cattle utilized while experiencing mild heat load. Data were collected from Angus X Hereford 2-year-old beef cows from UI herd over two years (37 grazing and walking minutes, 38 max slope). Genotypes were obtained using a Bovine GGP 50K SNP marker array and 41,686 markers were used in the analyses. Two SNPs on chromosome 11 are significantly (P = 5.01e-7, P = 6.46e-7) associated with grazing minutes and explain 0.52 proportion of variance (PVE). A SNP on chromosome 3 is significant for walking minutes (P=1.91e-6) with a PVE of 0.48. Additionally, a SNP on chromosome 14 is significantly (P = 8.50e-6) associated with max slope and has a PVE of 0.43. This ongoing project identified significant associations with grazing and walking minutes and maximum slope. This research will be strengthened with the addition of more animals over successive years. Some cattle spend more time grazing, walking, or at a higher elevation in mild heat load. Identifying genetic variants associated with grazing time, walking time, and maximum slope use while under heat stress can enable producers to select for cattle that best fit the rangeland available to them.

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Identifying genetic variants affecting cattle grazing behavior experiencing mild heat load

Translational Animal Science ◽

10.1093/tas/txab151 ◽

2021 ◽

Vol 5 (Supplement_S1) ◽

pp. S61-S66

Author(s):

Morgan R Stegemiller ◽

Melinda J Ellison ◽

John B Hall ◽

James E Sprinkle ◽

Brenda M Murdoch

Keyword(s):

Genetic Variants ◽

Heat Load ◽

Cattle Grazing ◽

Grazing Behavior ◽

Mild Heat

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Candidate gene scan for Single Nucleotide Polymorphisms involved in the determination of normal variability in human craniofacial morphology

10.1101/060814 ◽

2016 ◽

Author(s):

Mark Barash ◽

Philipp E. Bayer ◽

Angela van Daal

Keyword(s):

Single Nucleotide Polymorphisms ◽

Candidate Gene ◽

Genetic Variants ◽

Massively Parallel Sequencing ◽

Craniofacial Morphology ◽

Candidate Gene Approach ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Single Nucleotide ◽

Genome Wide

AbstractDespite intensive research on genetics of the craniofacial morphology using animal models and human craniofacial syndromes, the genetic variation that underpins normal human facial appearance is still largely elusive. Recent development of novel digital methods for capturing the complexity of craniofacial morphology in conjunction with high-throughput genotyping methods, show great promise for unravelling the genetic basis of such a complex trait.As a part of our efforts on detecting genomic variants affecting normal craniofacial appearance, we have implemented a candidate gene approach by selecting 1,201 single nucleotide polymorphisms (SNPs) and 4,732 tag SNPs in over 170 candidate genes and intergenic regions. We used 3-dimentional (3D) facial scans and direct cranial measurements of 587 volunteers to calculate 104 craniofacial phenotypes. Following genotyping by massively parallel sequencing, genetic associations between 2,332 genetic markers and 104 craniofacial phenotypes were tested.An application of a Bonferroni–corrected genome–wide significance threshold produced significant associations between five craniofacial traits and six SNPs. Specifically, associations of nasal width with rs8035124 (15q26.1), cephalic index with rs16830498 (2q23.3), nasal index with rs37369 (5q13.2), transverse nasal prominence angle with rs59037879 (10p11.23) and rs10512572 (17q24.3), and principal component explaining 73.3% of all the craniofacial phenotypes, with rs37369 (5p13.2) and rs390345 (14q31.3) were observed.Due to over-conservative nature of the Bonferroni correction, we also report all the associations that reached the traditional genome-wide p-value threshold (<5.00E-08) as suggestive. Based on the genome-wide threshold, 8 craniofacial phenotypes demonstrated significant associations with 34 intergenic and extragenic SNPs. The majority of associations are novel, except PAX3 and COL11A1 genes, which were previously reported to affect normal craniofacial variation.This study identified the largest number of genetic variants associated with normal variation of craniofacial morphology to date by using a candidate gene approach, including confirmation of the two previously reported genes. These results enhance our understanding of the genetics that determines normal variation in craniofacial morphology and will be of particular value in medical and forensic fields.Author SummaryThere is a remarkable variety of human facial appearances, almost exclusively the result of genetic differences, as exemplified by the striking resemblance of identical twins. However, the genes and specific genetic variants that affect the size and shape of the cranium and the soft facial tissue features are largely unknown. Numerous studies on animal models and human craniofacial disorders have identified a large number of genes, which may regulate normal craniofacial embryonic development.In this study we implemented a targeted candidate gene approach to select more than 1,200 polymorphisms in over 170 genes that are likely to be involved in craniofacial development and morphology. These markers were genotyped in 587 DNA samples using massively parallel sequencing and analysed for association with 104 traits generated from 3-dimensional facial images and direct craniofacial measurements. Genetic associations (p-values<5.00E-08) were observed between 8 craniofacial traits and 34 single nucleotide polymorphisms (SNPs), including two previously described genes and 26 novel candidate genes and intergenic regions. This comprehensive candidate gene study has uncovered the largest number of novel genetic variants affecting normal facial appearance to date. These results will appreciably extend our understanding of the normal and abnormal embryonic development and impact our ability to predict the appearance of an individual from a DNA sample in forensic criminal investigations and missing person cases.

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Genetic Variants behind Cardiovascular Diseases and Dementia

Genes ◽

10.3390/genes11121514 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1514

Author(s):

Wei-Min Ho ◽

Yah-Yuan Wu ◽

Yi-Chun Chen

Keyword(s):

White Matter ◽

Cardiovascular Diseases ◽

Genetic Variants ◽

White Matter Hyperintensities ◽

Association Studies ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Pubmed Database ◽

Risk Snps

Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand–receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments.

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Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip

Thrombosis and Haemostasis ◽

10.1160/th13-02-0087 ◽

2013 ◽

Vol 110 (11) ◽

pp. 995-1003 ◽

Cited By ~ 7

Author(s):

Sonia Shah ◽

Anna Guyatt ◽

Christophe Ladroue ◽

Meena Kumari ◽

Fotios Drenos ◽

...

Keyword(s):

Platelet Count ◽

Genetic Variants ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Pleiotropic Effect ◽

Plasma Viscosity ◽

Factor Vii ◽

Health Study ◽

Nucleotide Polymorphisms ◽

Genetic Associations

SummaryCoagulation phenotypes show strong intercorrelations, affect cardiovascular disease risk and are influenced by genetic variants. The objective of this study was to search for novel genetic variants influencing the following coagulation phenotypes: factor VII levels, fibrinogen levels, plasma viscosity and platelet count. We genotyped the British Women’s Heart and Health Study (n=3,445) and the Whitehall II study (n=5,059) using the Illumina HumanCVD BeadArray to investigate genetic associations and pleiotropy. In addition to previously reported associations (SH2B3, F7/F10, PROCR, GCKR, FGA/FGB/FGG, IL5), we identified novel associations at GRK5 (rs10128498, p = 1.30×10−6), GCKR (rs1260326, p = 1.63×10−6), ZNF259-APOA5 (rs651821, p = 7.17x10–6) with plasma viscosity; and at CSF1 (rs333948, p = 8.88×10−6) with platelet count. A pleiotropic effect was identified in GCKR which associated with factor VII (p = 2.16×10−7) and plasma viscosity (p = 1.63×10−6), and, to a lesser extent, ZNF259-APOA5 which also associated with factor VII and fibrinogen (p<1.00×10−2) and plasma viscosity (p<1.00×10−5). Triglyceride associated variants were overrepresented in factor VII and plasma viscosity associations. Adjusting for triglyceride levels resulted in attenuation of associations at the GCKR and ZNF259-APOA5 loci. In addition to confirming previously reported associations, we identified four single nucleotide polymorphisms (SNPs) associated with plasma viscosity and platelet count and found evidence of pleiotropic effects with SNPs in GCKR and ZNF259-APOA5. These triglyceride-associated, pleiotropic SNPs suggest a possible causal role for triglycerides in coagulation.

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Association of Genetic Variants With Migraine Subclassified by Clinical Symptoms in Adult Females

Frontiers in Neurology ◽

10.3389/fneur.2020.617472 ◽

2021 ◽

Vol 11 ◽

Author(s):

Joe Kossowsky ◽

Megan S. Schuler ◽

Franco Giulianini ◽

Charles B. Berde ◽

Ben Reis ◽

...

Keyword(s):

Genetic Variants ◽

Latent Class ◽

Clinical Symptoms ◽

Population Based ◽

Health Study ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Probable Migraine ◽

Diagnostic Symptoms ◽

Specific Symptoms

Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.

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Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers

Genes ◽

10.3390/genes12050686 ◽

2021 ◽

Vol 12 (5) ◽

pp. 686

Author(s):

Alireza Nazarian ◽

Alexander M. Kulminski

Keyword(s):

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Significance Level ◽

Association Analyses ◽

Complex Disorders ◽

Specific Effects ◽

Genome Wide ◽

Genetic Mechanisms ◽

Sex Disparities ◽

Almost All

Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at P < 5.0 × 10−6 neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.

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Common genetic variants and pathways in diabetes and associated complications and vulnerability of populations with different ethnic origins

Scientific Reports ◽

10.1038/s41598-021-86801-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sabrina Samad Shoily ◽

Tamim Ahsan ◽

Kaniz Fatema ◽

Abu Ashfaqur Sajib

Keyword(s):

Diabetes Mellitus ◽

Chronic Kidney Disease ◽

Genetic Variants ◽

Nucleotide Polymorphisms ◽

Differential Distribution ◽

East Asians ◽

Single Nucleotide ◽

Common Genetic Variants ◽

Haplotype Frequencies ◽

Variant Alleles

AbstractDiabetes mellitus is a complex and heterogeneous metabolic disorder which is often pre- or post-existent with complications such as cardiovascular disease, hypertension, inflammation, chronic kidney disease, diabetic retino- and nephropathies. However, the frequencies of these co-morbidities vary among individuals and across populations. It is, therefore, not unlikely that certain genetic variants might commonly contribute to these conditions. Here, we identified four single nucleotide polymorphisms (rs5186, rs1800795, rs1799983 and rs1800629 in AGTR1, IL6, NOS3 and TNFA genes, respectively) to be commonly associated with each of these conditions. We explored their possible interplay in diabetes and associated complications. The variant allele and haplotype frequencies at these polymorphic loci vary among different super-populations (African, European, admixed Americans, South and East Asians). The variant alleles are particularly highly prevalent in different European and admixed American populations. Differential distribution of these variants in different ethnic groups suggests that certain drugs might be more effective in selective populations rather than all. Therefore, population specific genetic architectures should be considered before considering a drug for these conditions.

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Genome-wide association analysis of metabolic syndrome quantitative traits in the GENNID multiethnic family study

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00670-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jia Y. Wan ◽

Deborah L. Goodman ◽

Emileigh L. Willems ◽

Alexis R. Freedland ◽

Trina M. Norden-Krichmar ◽

...

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Family Study ◽

Genome Wide Association ◽

European American ◽

Japanese American ◽

Genetic Associations ◽

Chromosome 11 ◽

Genome Wide ◽

American Families

Abstract Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our candidate linkage regions and were coincident within a gene or intergenic region, with two exceptions in European-American families: (a) within previously identified linkage region on chromosome 2, two significant GLI2-TFCP2L1 associations with weight, and (b) one chromosome 11 variant near CADM1-LINC00900 with pleiotropic blood pressure effects. Conclusions This multiethnic family study found genetic heterogeneity and coincident associations (with one case of pleiotropy), highlighting the importance of including diverse populations in genetic research and illustrating the complex genetic architecture underlying MetS.

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PSV-13 Genetic parameters and quantitative trait loci for heat stress related traits in sheep

Journal of Animal Science ◽

10.1093/jas/skaa054.289 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 163-164

Author(s):

Devin R Jacobs ◽

Claudia E Silvera-Rojas ◽

Jennifer M Bormann ◽

Terry A Gipson ◽

Arthur L Goetsch ◽

...

Keyword(s):

Heat Stress ◽

Quantitative Trait Loci ◽

Rectal Temperature ◽

Quantitative Trait ◽

Fixed Effects ◽

Univariate Analysis ◽

Average Daily Gain ◽

The United States ◽

Nucleotide Polymorphisms ◽

Trait Loci

Abstract Greater selection emphasis has been placed on efficiency than on fitness in livestock populations over the last several decades. Heat stress is a concern in production systems due to the negative effects on production, reproduction, and immunity. The objective of the study was to estimate variance components and identify quantitative trait loci (QTL) for heat stress related traits in sheep. A total of 125 Dorper, Katahdin, and St. Croix ewes originating from four regions of the United States were selected for the experiment. Animals were separated into four trials due to facility limitations. Data were collected for each trial over four consecutive two-week periods in an environmentally controlled facility with targeted heat load index (HLI) for daytime/nighttime of 70/70, 85/77, 90/77, and 95/81. Body weight was collected three times per week and rectal temperature was collected weekly. Black globe temperature and humidity were measured every 15 minutes. Animals were genotyped using the Illumina OvineSNP50 BeadChip. After quality control, 49,396 effective single nucleotide polymorphisms were included in the univariate analysis performed with the BLUPF90 suite of programs. Fixed effects in the models included region of origin, breed, trial, and age as a covariate. Traits analyzed included rectal temperature at 95 HLI (RT95), feed intake at 95 HLI (FI95), and average daily gain for the period for HLI between 90 and 95 (ADG). Heritabilities for RT95, FI95, and ADG were 0.35, 0.10, and 0.10, respectively. Largest effect QTL were identified on chromosomes 23, 9, and 6 for RT95, chromosomes 9, 2, and 20 for FI95, and chromosomes 6, 1, and 5 for ADG. Many of the regions identified have also been associated with weight and carcass traits in other studies, but few had obvious connections to the heat stress related response. In conclusion, results suggest selection could improve heat tolerance in sheep.

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Transporters, TBC1D4, and ARID5B Variants to Explain Glycated Hemoglobin Variability in Patients with Type 2 Diabetes

Pharmacology ◽

10.1159/000517462 ◽

2021 ◽

pp. 1-9

Author(s):

Vanessa Gonzalez-Covarrubias ◽

Héctor Sánchez-Ibarra ◽

Karla Lozano-Gonzalez ◽

Sergio Villicaña ◽

Tomas Texis ◽

...

Keyword(s):

Genetic Variants ◽

Glucose Control ◽

Plasma Levels ◽

Prediction Models ◽

Glycated Hemoglobin ◽

Clinical Chemistry ◽

Diabetic Patients ◽

Genetic Associations ◽

Hemoglobin Variability

Introduction: Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. Methods: HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. Results: We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. Conclusions: Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.

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