scholarly journals snpGeneSets: An R Package for Genome-Wide Study Annotation

2016 ◽  
Vol 6 (12) ◽  
pp. 4087-4095 ◽  
Author(s):  
Hao Mei ◽  
Lianna Li ◽  
Fan Jiang ◽  
Jeannette Simino ◽  
Michael Griswold ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
R Package ◽  
Knowledge Bases ◽  
Gene Expressions ◽  
Next Generation Sequencing Technology ◽  
Gene Sets ◽  
Genome Wide ◽  
A Genome ◽  
Downstream Analysis

Abstract Genome-wide studies (GWS) of SNP associations and differential gene expressions have generated abundant results; next-generation sequencing technology has further boosted the number of variants and genes identified. Effective interpretation requires massive annotation and downstream analysis of these genome-wide results, a computationally challenging task. We developed the snpGeneSets package to simplify annotation and analysis of GWS results. Our package integrates local copies of knowledge bases for SNPs, genes, and gene sets, and implements wrapper functions in the R language to enable transparent access to low-level databases for efficient annotation of large genomic data. The package contains functions that execute three types of annotations: (1) genomic mapping annotation for SNPs and genes and functional annotation for gene sets; (2) bidirectional mapping between SNPs and genes, and genes and gene sets; and (3) calculation of gene effect measures from SNP associations and performance of gene set enrichment analyses to identify functional pathways. We applied snpGeneSets to type 2 diabetes (T2D) results from the NHGRI genome-wide association study (GWAS) catalog, a Finnish GWAS, and a genome-wide expression study (GWES). These studies demonstrate the usefulness of snpGeneSets for annotating and performing enrichment analysis of GWS results. The package is open-source, free, and can be downloaded at: https://www.umc.edu/biostats_software/.

scholarly journals Genome-wide association study of treatment-resistance in depression and meta-analysis of three independent samples

2018 ◽  
Vol 214 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Chiara Fabbri ◽  
Siegfried Kasper ◽  
Alexander Kautzky ◽  
Lucie Bartova ◽  
Markus Dold ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Adenosine Monophosphate ◽  
Research Support ◽  
Antidepressant Treatments ◽  
Advisory Boards ◽  
Gene Sets ◽  
Genome Wide ◽  
A Genome ◽  
Resistant Depression

BackgroundTreatment-resistant depression (TRD) is the most problematic outcome of depression in terms of functional impairment, suicidal thoughts and decline in physical health.AimsTo investigate the genetic predictors of TRD using a genome-wide approach to contribute to the development of precision medicine.MethodA sample recruited by the European Group for the Study of Resistant Depression (GSRD) including 1148 patients with major depressive disorder (MDD) was characterised for the occurrence of TRD (lack of response to at least two adequate antidepressant treatments) and genotyped using the Infinium PsychArray. Three clinically relevant patient groups were considered: TRD, responders and non-responders to the first antidepressant trial, thus outcomes were based on comparisons of these groups. Genetic analyses were performed at the variant, gene and gene-set (i.e. functionally related genes) level. Additive regression models of the outcomes and relevant covariates were used in the GSRD participants and in a fixed-effect meta-analysis performed between GSRD, STAR*D (n = 1316) and GENDEP (n = 761) participants.ResultsNo individual polymorphism or gene was associated with TRD, although some suggestive signals showed enrichment in cytoskeleton regulation, transcription modulation and calcium signalling. Two gene sets (GO:0043949 and GO:0000183) were associated with TRD versus response and TRD versus response and non-response to the first treatment in the GSRD participants and in the meta-analysis, respectively (corrected P = 0.030 and P = 0.027).ConclusionsThe identified gene sets are involved in cyclic adenosine monophosphate mediated signal and chromatin silencing, two processes previously implicated in antidepressant action. They represent possible biomarkers to implement personalised antidepressant treatments and targets for new antidepressants.Declaration of interestD.S. has received grant/research support from GlaxoSmithKline and Lundbeck; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen and Lundbeck. S.M. has been a consultant or served on advisory boards for: AstraZeneca, Bristol-Myers Squibb, Forest, Johnson & Johnson, Leo, Lundbeck, Medelink, Neurim, Pierre Fabre, Richter. S.K. has received grant/research support from Eli Lilly, Lundbeck, Bristol-Myers Squibb, GlaxoSmithKline, Organon, Sepracor and Servier; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Lundbeck, Pfizer, Organon, Schwabe, Sepracor, Servier, Janssen and Novartis; and has served on speakers' bureaus for AstraZeneca, Eli Lily, Lundbeck, Schwabe, Sepracor, Servier, Pierre Fabre, Janssen and Neuraxpharm. J.Z. has received grant/research support from Lundbeck, Servier, Brainsway and Pfizer, has served as a consultant or on advisory boards for Servier, Pfizer, Abbott, Lilly, Actelion, AstraZeneca and Roche and has served on speakers' bureaus for Lundbeck, Roch, Lilly, Servier, Pfizer and Abbott. J.M. is a member of the Board of the Lundbeck International Neuroscience Foundation and of Advisory Board of Servier. A.S. is or has been consultant/speaker for: Abbott, AbbVie, Angelini, Astra Zeneca, Clinical Data, Boehringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi and Servier. C.M.L. receives research support from RGA UK Services Limited.

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 Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population

2020 ◽  
Vol 37 (5) ◽  
pp. 1306-1316 ◽  
Author(s):  
Yoshiaki Yasumizu ◽  
Saori Sakaue ◽  
Takahiro Konuma ◽  
Ken Suzuki ◽  
Koichi Matsuda ◽  
...  
Keyword(s):  
Natural Selection ◽  
Japanese Population ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Recent Common Ancestor ◽  
Selection Signatures ◽  
Most Recent Common Ancestor ◽  
Genome Wide ◽  
A Genome

Abstract Elucidation of natural selection signatures and relationships with phenotype spectra is important to understand adaptive evolution of modern humans. Here, we conducted a genome-wide scan of selection signatures of the Japanese population by estimating locus-specific time to the most recent common ancestor using the ascertained sequentially Markovian coalescent (ASMC), from the biobank-based large-scale genome-wide association study data of 170,882 subjects. We identified 29 genetic loci with selection signatures satisfying the genome-wide significance. The signatures were most evident at the alcohol dehydrogenase (ADH) gene cluster locus at 4q23 (PASMC = 2.2 × 10−36), followed by relatively strong selection at the FAM96A (15q22), MYOF (10q23), 13q21, GRIA2 (4q32), and ASAP2 (2p25) loci (PASMC &lt; 1.0 × 10−10). The additional analysis interrogating extended haplotypes (integrated haplotype score) showed robust concordance of the detected signatures, contributing to fine-mapping of the genes, and provided allelic directional insights into selection pressure (e.g., positive selection for ADH1B-Arg48His and HLA-DPB1*04:01). The phenome-wide selection enrichment analysis with the trait-associated variants identified a variety of the modern human phenotypes involved in the adaptation of Japanese. We observed population-specific evidence of enrichment with the alcohol-related phenotypes, anthropometric and biochemical clinical measurements, and immune-related diseases, differently from the findings in Europeans using the UK Biobank resource. Our study demonstrated population-specific features of the selection signatures in Japanese, highlighting a value of the natural selection study using the nation-wide biobank-scale genome and phenotype data.

scholarly journals Genome-Wide Association Study (GWAS) of Mesocotyl Length for Direct Seeding in Rice

Agronomy ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2527
Author(s):  
Seong-Gyu Jang ◽  
So-Yeon Park ◽  
San Mar Lar ◽  
Hongjia Zhang ◽  
Ah-Rim Lee ◽  
...  
Keyword(s):  
Association Study ◽  
Candidate Genes ◽  
Genome Wide Association Study ◽  
Direct Seeding ◽  
Genome Wide Association ◽  
Matrix Analysis ◽  
Labor Costs ◽  
Gene Expressions ◽  
Genome Wide ◽  
A Genome

Direct seeding is considered an efficient cultivation technology that reduces water use and labor costs. Mesocotyl length is one of the significant traits in cultivation; long mesocotyl is beneficial for the rate and uniformity of seedling emergence. In this study, we used a core collection of 137 rice accessions to identify quantitative trait loci (QTL) for mesocotyl elongation. A genome-wide association study (GWAS), combined with a principal component analysis (PCA) and a kinship matrix analysis, was conducted for the genotype analysis of 2 million, high-quality single nucleotide polymorphisms (SNPs). Through this GWAS analysis, 11 lead SNPs were confirmed to be associated with mesocotyl length, and a linkage disequilibrium (LD) decay analysis identified the 230 kb exploratory range for the detection of QTLs and candidate genes. Based on the gene expression database and haplotype analysis, five candidate genes (Os01g0269800, Os01g0731100, Os08g0136700, Os08g0137800, and Os08g0137900) were detected to be significantly associated with phenotypic variation. Five candidate gene expressions are reported to be associated with various plant hormone responses. Interestingly, two biotic stress response genes and two copper-containing redox proteins were detected as the candidate genes. The results of this study provide associated SNPs in candidate genes for mesocotyl length and strategies for developing direct seeding in breeding programs.

scholarly journals Eagle for better genome-wide association mapping

2021 ◽  
Author(s):  
Andrew W George ◽  
Arunas Verbyla ◽  
Joshua Bowden
Keyword(s):  
Association Mapping ◽  
Genome Wide Association Study ◽  
R Package ◽  
Study Data ◽  
Single Locus ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Trait Associations

Abstract Eagle is an R package for multi-locus association mapping on a genome-wide scale. It is unlike other multi-locus packages in that it is easy-to-use for R users and non-users alike. It has two modes of use, command line and GUI. Eagle is fully documented and has its own supporting website, http://eagle.r-forge.r-project.org/index.html. Eagle is a significant improvement over the method-of-choice, single-locus association mapping. It has greater power to detect SNP-trait associations. It is based on model selection, linear mixed models, and a clever idea on how random effects can be used to identify SNP-trait associations. Through an example with real mouse data, we demonstrate Eagle’s ability to bring clarity and increased insight to single-locus findings. Initially, we see Eagle complementing single-locus analyses. However, over time, we hope the community will make, increasingly, multi-locus association mapping their method-of-choice for the analysis of genome-wide association study data.

scholarly journals A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1804
Author(s):  
Seong-Beom Cho ◽  
Jinhwa Jang
Keyword(s):  
Blood Pressure ◽  
Association Study ◽  
Genetic Susceptibility ◽  
Genetic Heterogeneity ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Heterogeneity Analysis

Genome-wide association studies have expanded our understanding of the genetic variation of hypertension. Hypertension and blood pressure are influenced by sex-specific differences; therefore, genetic variants may have sex-specific effects on phenotype. To identify the genetic factors influencing the sex-specific differences concerning hypertension, we conducted a heterogeneity analysis of a genome-wide association study (GWAS) on 13,926 samples from a Korean population. Using the Illumina exome chip data of the population, we performed GWASs of the male and female population independently and applied a statistical test that identified heterogeneous effects of the variants between the two groups. To gain information about the biological implication of the genetic heterogeneity, we used gene set enrichment analysis with GWAS catalog and pathway gene sets. The heterogeneity analysis revealed that the rs11066015 of ACAD10 was a significant locus that had sex-specific genetic effects on the development of hypertension. The rs2074356 of HECTD4 also showed significant genetic heterogeneity in systolic blood pressure. The enrichment analysis showed significant results that are consistent with the pathophysiology of hypertension. These results indicate a sex-specific genetic susceptibility to hypertension that should be considered in future genetic studies of hypertension.

scholarly journals Genomic Regions Associated with Fusarium Wilt Resistance in Flax

2021 ◽  
Vol 22 (22) ◽  
pp. 12383
Author(s):  
Alexander Kanapin ◽  
Mikhail Bankin ◽  
Tatyana Rozhmina ◽  
Anastasia Samsonova ◽  
Maria Samsonova
Keyword(s):  
Fusarium Wilt ◽  
Genome Wide Association Study ◽  
Plant Immunity ◽  
R Package ◽  
Chromosome 1 ◽  
Research Centre ◽  
Potential Candidate ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Modern flax cultivars are susceptible to many diseases; arguably, the most economically damaging of these is the Fusarium wilt fungal disease. Over the past decades international flax breeding initiatives resulted in the development of resistant cultivars. However, much remains to be learned about the mechanisms of resistance to Fusarium infection in flax. As a first step to uncover the genetic factors associated with resistance to Fusarium wilt disease, we performed a genome-wide association study (GWAS) using 297 accessions from the collection of the Federal Research Centre of the Bast Fiber Crops, Torzhok, Russia. These genotypes were infected with a highly pathogenic Fusarium oxysporum f.sp. lini MI39 strain; the wilt symptoms were documented in the course of three successive years. Six different single-locus models implemented in GAPIT3 R package were applied to a selected subset of 72,526 SNPs. A total of 15 QTNs (Quantitative Trait Nucleotides) were detected during at least two years of observation, while eight QTNs were found during all three years of the experiment. Of these, ten QTNs occupied a region of 640 Kb at the start of chromosome 1, while the remaining QTNs mapped to chromosomes 8, 11 and 13. All stable QTNs demonstrate a statistically significant allelic effect across 3 years of the experiment. Importantly, several QTNs spanned regions that harbored genes involved in the pathogen recognition and plant immunity response, including the KIP1-like protein (Lus10025717) and NBS-LRR protein (Lus10025852). Our results provide novel insights into the genetic architecture of flax resistance to Fusarium wilt and pinpoint potential candidate genes for further in-depth studies.

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