scholarly journals Genes and Pathways Affecting Sheep Productivity Traits: Genetic Parameters, Genome-Wide Association Mapping, and Pathway Enrichment Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Seyed Mehdi Esmaeili-Fard ◽  
Mohsen Gholizadeh ◽  
Seyed Hasan Hafezian ◽  
Rostam Abdollahi-Arpanahi
Keyword(s):  
Ion Transport ◽  
Calcium Ion ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Meat Production ◽  
Pathway Enrichment Analysis ◽  
Litter Weight ◽  
Genome Wide ◽  
Calcium Ion Transport

Ewe productivity is a composite and maternal trait that is considered the most important economic trait in sheep meat production. The objective of this study was the application of alternative genome-wide association study (GWAS) approaches followed by gene set enrichment analysis (GSEA) on the ewes’ genome to identify genes affecting pregnancy outcomes and lamb growth after parturition in Iranian Baluchi sheep. Three maternal composite traits at birth and weaning were considered. The traits were progeny birth weight, litter mean weight at birth, total litter weight at birth, progeny weaning weight, litter mean weight at weaning, and total litter weight at weaning. GWASs were performed on original phenotypes as well as on estimated breeding values. The significant SNPs associated with composite traits at birth were located within or near genes RDX, FDX1, ARHGAP20, ZC3H12C, THBS1, and EPG5. Identified genes and pathways have functions related to pregnancy, such as autophagy in the placenta, progesterone production by the placenta, placental formation, calcium ion transport, and maternal immune response. For composite traits at weaning, genes (NR2C1, VEZT, HSD17B4, RSU1, CUBN, VIM, PRLR, and FTH1) and pathways affecting feed intake and food conservation, development of mammary glands cytoskeleton structure, and production of milk components like fatty acids, proteins, and vitamin B-12, were identified. The results show that calcium ion transport during pregnancy and feeding lambs by milk after parturition can have the greatest impact on weight gain as compared to other effects of maternal origin.

scholarly journals Maternal genes and pathways affecting birth weight and weaning weight traits in sheep: A GWAS and pathway enrichment analysis

2020 ◽  
Author(s):  
Mehdi Esmaeilifard ◽  
Seyed Hasan Hafezian ◽  
Mohsen Gholizadeh ◽  
Rostam Abdollahi-Arpanahi
Keyword(s):  
Immune Response ◽  
Birth Weight ◽  
Ion Transport ◽  
Calcium Ion ◽  
Enrichment Analysis ◽  
Mammary Glands ◽  
Gene Set Enrichment Analysis ◽  
Weaning Weight ◽  
Litter Weight ◽  
Milk Components

Abstract Background Ewe productivity is considered as the most important economic trait in sheep meat production. Due to very limited reports, the objective of this study was the application of alternative GWAS approaches followed by gene set enrichment analysis (GSEA) on the maternal genome to unravel the genomic architecture underlying ewe productivity in Iranian Baluchi sheep. Six maternal composite traits including progeny birth weight (PBW), litter mean weight at birth (LMWB), total litter weight at birth (TLWB), progeny weaning weight (PWW), litter mean weight at weaning (LMWW) and total litter weight at weaning (TLWW) were studied. Results Genes such as RDX , FDX1 , ARHGAP20 , ZC3H12C , THBS1 , and EPG5 on OAR6, OAR7, OAR15, and OAR23 were identified for composite traits at birth. The genes are involved in pregnancy, including autophagy in the placenta, progesterone production by the placenta, maternal immune response and placenta formation. Some maternal pathways, related to calcium ion transport, signal transduction, neurogenesis, and immune response were also identified for birth weight traits. Moreover, many genes including NR2C1 , VEZT , HSD17B4 , RSU1 , CUBN , VIM , PRLR , and FTH1 were located on OAR2, OAR3, OAR5, OAR7, OAR13, OAR16, and OAR25 identified as maternal genes affecting weaning weight traits. Most of the identified genes were involved in mammary glands development and milk components production. Also, many GO terms related to protein processing and transport, ion transport and homeostasis, proteins and lipid phosphorylation, and phospholipid translocation were identified in association with weaning weight traits. Conclusions The results of the present study revealed that calcium ion homeostasis and transport and the maternal immune system could have an important role in progeny’s birth weight. Also, the results showed that genes and pathways affecting mammary glands development during pregnancy and milk components production have the most impact on lambs weaning weight. These findings contribute to a better understanding of the genetic architecture of the studied traits and providing opportunities for improving ewe productivity via marker-assisted selection.

scholarly journals Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Emrin Horgusluoglu-Moloch ◽  
◽  
Shannon L. Risacher ◽  
Paul K. Crane ◽  
Derrek Hibar ◽  
...  
Keyword(s):  
Association Analysis ◽  
Adult Neurogenesis ◽  
Enrichment Analysis ◽  
Hippocampal Volume ◽  
Imaging Genetics ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Genome Wide

Abstract Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer’s Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.

scholarly journals SNP-based pathway enrichment analysis for genome-wide association studies

2011 ◽  
Vol 12 (1) ◽  
pp. 99 ◽  
Author(s):  
Lingjie Weng ◽  
Fabio Macciardi ◽  
Aravind Subramanian ◽  
Guia Guffanti ◽  
Steven G Potkin ◽  
...  
Keyword(s):  
Association Studies ◽  
Enrichment Analysis ◽  
Genome Wide Association ◽  
Pathway Enrichment Analysis ◽  
Genome Wide Association Studies ◽  
Pathway Enrichment ◽  
Genome Wide

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 Importance of SNP Dependency Correction and Association Integration for Gene Set Analysis in Genome-Wide Association Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Michal Marczyk ◽  
Agnieszka Macioszek ◽  
Joanna Tobiasz ◽  
Joanna Polanska ◽  
Joanna Zyla
Keyword(s):  
Association Studies ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Gene Set Analysis ◽  
Genome Wide Association Studies ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Genome Wide ◽  
The Impact

A typical genome-wide association study (GWAS) analyzes millions of single-nucleotide polymorphisms (SNPs), several of which are in a region of the same gene. To conduct gene set analysis (GSA), information from SNPs needs to be unified at the gene level. A widely used practice is to use only the most relevant SNP per gene; however, there are other methods of integration that could be applied here. Also, the problem of nonrandom association of alleles at two or more loci is often neglected. Here, we tested the impact of incorporation of different integrations and linkage disequilibrium (LD) correction on the performance of several GSA methods. Matched normal and breast cancer samples from The Cancer Genome Atlas database were used to evaluate the performance of six GSA algorithms: Coincident Extreme Ranks in Numerical Observations (CERNO), Gene Set Enrichment Analysis (GSEA), GSEA-SNP, improved GSEA for GWAS (i-GSEA4GWAS), Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA), and Over-Representation Analysis (ORA). Association of SNPs to phenotype was calculated using modified McNemar’s test. Results for SNPs mapped to the same gene were integrated using Fisher and Stouffer methods and compared with the minimum p-value method. Four common measures were used to quantify the performance of all combinations of methods. Results of GSA analysis on GWAS were compared to the one performed on gene expression data. Comparing all evaluation metrics across different GSA algorithms, integrations, and LD correction, we highlighted CERNO, and MAGENTA with Stouffer as the most efficient. Applying LD correction increased prioritization and specificity of enrichment outcomes for all tested algorithms. When Fisher or Stouffer were used with LD, sensitivity and reproducibility were also better. Using any integration method was beneficial in comparison with a minimum p-value method in specific combinations. The correlation between GSA results from genomic and transcriptomic level was the highest when Stouffer integration was combined with LD correction. We thoroughly evaluated different approaches to GSA in GWAS in terms of performance to guide others to select the most effective combinations. We showed that LD correction and Stouffer integration could increase the performance of enrichment analysis and encourage the usage of these techniques.

scholarly journals Genome-Wide Association Analysis Identified ANXA1 Associated with Shoulder Impingement Syndrome in UK Biobank Samples

2020 ◽  
Vol 10 (9) ◽  
pp. 3279-3284
Author(s):  
Bolun Cheng ◽  
Yujie Ning ◽  
Chujun Liang ◽  
Ping Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Impingement Syndrome ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Genetic Mechanism ◽  
Shoulder Impingement Syndrome ◽  
Uk Biobank ◽  
Shoulder Impingement ◽  
Genome Wide

Abstract Shoulder impingement syndrome (SIS) is a common shoulder disorder with unclear genetic mechanism. In this study, Genome-wide Association Study (GWAS) was conducted to identify the candidate loci associated with SIS by using the UK Biobank samples (including 3,626 SIS patients and 3,626 control subjects). Based on the GWAS results, gene set enrichment analysis was further performed to detect the candidate gene ontology and pathways associated with SIS. We identified multiple risk loci associated with SIS, such as rs750968 (P = 4.82 × 10−8), rs754832 (P = 4.83 × 10−8) and rs1873119 (P = 6.39 × 10−8) of ANXA1 gene. Some candidate pathways have been identified related to SIS, including those linked to infection response and hypoxia, “ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN” (P = 0.012) and “MANALO_HYPOXIA_UP” (P = 5.00 × 10−5). Our results provide novel clues for understanding the genetic mechanism of SIS.

Sign in / Sign up

Export Citation Format

Share Document