scholarly journals A brief overview of GWAS: discover genetic variations of diseases and phenotypes

2020 ◽  
Vol 185 ◽  
pp. 03014
Author(s):  
Zhiying Peng
Keyword(s):  
Large Scale ◽  
Genome Wide Association Study ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
Information Discovery ◽  
Genome Wide ◽  
Whole Genomes ◽  
Statistical Analysis Method ◽  
History Of ◽  
Application Fields

GWAS, or Genome-wide association study, is a statistical analysis method to reveal specific genetic variations, usually single nucleotide polymorphisms, with particular phenotypes or diseases. The power to scan whole genomes from large scale samples made the method an efficient tool for information discovery. In the last decades, the application of GWAS has flourished, which benefited our understanding related to diseases, breeding and many other topics. In this review, we overviewed the history of GWAS, as well as different approaches to perform the analysis under different circumstances during different stages. Meanwhile, we also showed how different GWAS approaches benefited diverse research and application fields, and the potential limitations of the method.

scholarly journals Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum

2018 ◽  
Vol 78 (09) ◽  
pp. 866-870 ◽  
Author(s):  
Marlena Fejzo ◽  
Daria Arzy ◽  
Rayna Tian ◽  
Kimber MacGibbon ◽  
Patrick Mullin
Keyword(s):  
Genome Wide Association Study ◽  
Risk Allele ◽  
Hyperemesis Gravidarum ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Severe Nausea ◽  
Single Nucleotide ◽  
Genome Wide ◽  
History Of ◽  
Study Support

Abstract Introduction Hyperemesis gravidarum (HG), a pregnancy complication characterized by severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies. It is associated with both maternal and fetal morbidity. HG is highly heritable and recurs in approximately 80% of women. In a recent genome-wide association study, it was shown that placentation, appetite, and the cachexia gene GDF15 are linked to HG. The purpose of this study was to explore whether GDF15 alleles linked to overexpression of GDF15 protein segregate with the condition in families, and whether the GDF15 risk allele is associated with recurrence of HG. Methods We analyzed GDF15 overexpression alleles for segregation with disease using exome-sequencing data from 5 HG families. We compared the allele frequency of the GDF15 risk allele, rs16982345, in patients who had recurrence of HG with its frequency in those who did not have recurrence. Results Single nucleotide polymorphisms (SNPs) linked to higher levels of GDF15 segregated with disease in HG families. The GDF15 risk allele, rs16982345, was associated with an 8-fold higher risk of recurrence of HG. Conclusion The findings of this study support the hypothesis that GDF15 is involved in the pathogenesis of both familial and recurrent cases of HG. The findings may be applicable when counseling women with a familial history of HG or recurrent HG. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under development. Based on our findings, patients carrying GDF15 variants associated with GDF15 overexpression should be included in future studies of GDF15-GFRAL-based therapeutics. If safe, this approach could reduce maternal and fetal morbidity.

Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort

2019 ◽  
Vol 54 (9) ◽  
pp. 902-908 ◽  
Author(s):  
Xiaoman Liu ◽  
Siew-Kee Low ◽  
Joshua R Atkins ◽  
Jing Qin Wu ◽  
William R Reay ◽  
...  
Keyword(s):  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Receptor Gene ◽  
Genome Wide Association ◽  
Polymorphism Analysis ◽  
Snp Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide

Objectives: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. Methods: We performed a case–control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. Results: The strongest finding ( p = 2.01 × 10−6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance ( p = 2.78 × 10−6). Conclusion: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.

scholarly journals Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL

Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1911-1916 ◽  
Author(s):  
Susan L. Slager ◽  
Kari G. Rabe ◽  
Sara J. Achenbach ◽  
Celine M. Vachon ◽  
Lynn R. Goldin ◽  
...  
Keyword(s):  
Family History ◽  
Genome Wide Association Study ◽  
Statistical Significance ◽  
Familial Risk ◽  
Lymphocytic Leukemia ◽  
Genome Wide Association ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
History Of

Abstract Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values ≤ 3.37 × 10−8), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 × 10−9). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies.

scholarly journals GWAS identifies nine nephrolithiasis susceptibility loci related with metabolic metabolic and crystallization pathways

2019 ◽  
Author(s):  
Chizu Tanikawa ◽  
Yoichiro Kamatani ◽  
Chikashi Terao ◽  
Masayuki Usami ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Genetic Background ◽  
Quantitative Traits ◽  
Large Scale ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Genetic Variations ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
Host Genetic ◽  
Host Genetic Factors

ABSTRACTNephrolithiasis is a common urological trait disorder with acute pain. Although previous studies have identified various genetic variations associated with nephrolithiasis, the host genetic factors remain largely unidentified. To identify novel nephrolithiasis loci in the Japanese population, we performed large-scale GWAS (Genome wide association study) using 11,130 cases and 187,639 controls, followed by a replication analysis using 2,289 cases and 3,817 controls. The analysis identified 14 significant loci, including 9 novel loci on 2p23.2-3, 6p21.2, 6p12.3, 6q23.2, 16p12.3, 16q12.2, 17q23.2, 19p13.12, and 20q13.2. Interestingly, 10 of the 14 regions showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic background among nephrolithiasis patients and these quantitative traits. Four novel loci are related to the metabolic pathway, while the remaining 10 loci are associated with the crystallization pathway. Our findings demonstrate the crucial roles of genetic variations in the development of nephrolithiasis.SIGNIFICANCE STATEMENTNephrolithiasis is a common urothelial disorders with frequent recurrence rate, but its genetic background is largely remained unidentified. Previous GWAS identified 6 genetic factors in total. Here we performed a GWAS using more than 200,000 samples in the Japanese populations, and identified 14 significant loci and nine of them are novel. We also found that 10 of the 14 loci showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (BMI, eGFR, UA, Ca etc). All 14 significant loci are associate with either metabolic or crystallization pathways. Thus, our findings elucidated the underlying molecular pathogenesis of nephrolithiasis.

scholarly journals Association Analysis ofNALCNPolymorphisms rs1338041 and rs61973742 in a Chinese Population with Isolated Cervical Dystonia

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Qingqing Zhou ◽  
Jing Yang ◽  
Bei Cao ◽  
Yongping Chen ◽  
Qianqian Wei ◽  
...  
Keyword(s):  
Cervical Dystonia ◽  
Chinese Population ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Positive Family History ◽  
Asian Population ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome ◽  
History Of

Background. A genome-wide association study (GWAS) demonstrated a possible association between cervical dystonia (CD) and a sodium leak channel, nonselective (NALCN) gene. However, the association betweenNALCNand CD was largely unknown in Asian population. The present study was carried out to examine the associations between the two single nucleotide polymorphisms (SNPs) rs1338041 and rs61973742 in theNALCNgene and CD in a Chinese population.Methods. In a cohort of 201 patients with isolated CD, we genotyped the two SNPs rs1338041 and rs61973742 using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). We also included 289 unrelated, age- and sex-matched healthy controls (HCs) from the same region.Result. No significant differences were observed in either the genotype distributions or the minor allele frequencies (MAFs) of the two SNPs between the CD patients and the HCs. There were no significant differences between early-onset and late-onset CD patients, between patients with and without a positive family history of dystonia, or between patients with and without tremor or sensory tricks.Conclusion. Lack of association between the SNPs ofNALCNand CD suggests that the SNPs ofNALCNdo not play a role in CD in a Chinese population.

scholarly journals Tracing founder haplotypes of Japanese apple varieties: application in genomic prediction and genome-wide association study

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Mai F. Minamikawa ◽  
Miyuki Kunihisa ◽  
Koji Noshita ◽  
Shigeki Moriya ◽  
Kazuyuki Abe ◽  
...  
Keyword(s):  
Association Study ◽  
Genomic Prediction ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Quality Traits ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Fruit Quality Traits ◽  
History Of

AbstractHaplotypes provide useful information for genomics-based approaches, genomic prediction, and genome-wide association study. As a small number of superior founders have contributed largely to the breeding history of fruit trees, the information of founder haplotypes may be relevant for performing the genomics-based approaches in these plants. In this study, we proposed a method to estimate 14 haplotypes from 7 founders and automatically trace the haplotypes forward to apple parental (185 varieties) and breeding (659 F1 individuals from 16 full-sib families) populations based on 11,786 single-nucleotide polymorphisms, by combining multiple algorithms. Overall, 92% of the single-nucleotide polymorphisms information in the parental and breeding populations was characterized by the 14 founder haplotypes. The use of founder haplotype information improved the accuracy of genomic prediction in 7 traits and the resolution of genome-wide association study in 13 out of 27 fruit quality traits analyzed in this study. We also visualized the significant propagation of the founder haplotype with the largest genetic effect in genome-wide association study over the pedigree tree of the parental population. These results suggest that the information of founder haplotypes can be useful for not only genetic improvement of fruit quality traits in apples but also for understanding the selection history of founder haplotypes in the breeding program of Japanese apple varieties.

scholarly journals Comprehensive Genome-Wide Association Analysis Reveals the Genetic Basis of Root System Architecture in Soybean

2020 ◽  
Vol 11 ◽  
Author(s):  
Waldiodio Seck ◽  
Davoud Torkamaneh ◽  
François Belzile
Keyword(s):  
Root System ◽  
System Architecture ◽  
Phenotypic Variation ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Primary Root ◽  
Root System Architecture ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

Increasing the understanding genetic basis of the variability in root system architecture (RSA) is essential to improve resource-use efficiency in agriculture systems and to develop climate-resilient crop cultivars. Roots being underground, their direct observation and detailed characterization are challenging. Here, were characterized twelve RSA-related traits in a panel of 137 early maturing soybean lines (Canadian soybean core collection) using rhizoboxes and two-dimensional imaging. Significant phenotypic variation (P < 0.001) was observed among these lines for different RSA-related traits. This panel was genotyped with 2.18 million genome-wide single-nucleotide polymorphisms (SNPs) using a combination of genotyping-by-sequencing and whole-genome sequencing. A total of 10 quantitative trait locus (QTL) regions were detected for root total length and primary root diameter through a comprehensive genome-wide association study. These QTL regions explained from 15 to 25% of the phenotypic variation and contained two putative candidate genes with homology to genes previously reported to play a role in RSA in other species. These genes can serve to accelerate future efforts aimed to dissect genetic architecture of RSA and breed more resilient varieties.

scholarly journals Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color

2021 ◽  
Vol 7 (11) ◽  
pp. eabd1239
Author(s):  
Mark Simcoe ◽  
Ana Valdes ◽  
Fan Liu ◽  
Nicholas A. Furlotte ◽  
David M. Evans ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Color Variation ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Melanin Pigmentation ◽  
Eye Color ◽  
Human Eye ◽  
Genome Wide ◽  
Genomic Regions

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

scholarly journals Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Archana Khadgi ◽  
Courtney A. Weber
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genomic Region ◽  
Rubus Idaeus ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Red Raspberry ◽  
Genome Wide ◽  
A Genome ◽  
Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

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