scholarly journals Genetic Basis of Maize Resistance to Multiple-Insect Pests: Integrated Genome-Wide Comparative Mapping and Candidate Gene Prioritization

2020 ◽  
Author(s):  
Arfang BADJI ◽  
Daniel Bomet KWEMOI ◽  
Lewis MACHIDA ◽  
Dennis OKII ◽  
Natasha MWILA ◽  
...  
Keyword(s):  
Insect Resistance ◽  
Defense Mechanisms ◽  
Genome Wide Association Study ◽  
Insect Pests ◽  
Physical Map ◽  
Nucleotide Polymorphisms ◽  
Multiple Traits ◽  
Significance Level ◽  
Mapping Panel ◽  
Genome Wide

Several herbivores feed on maize in field and storage setups making the development of multiple-insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to FAW whilst bulked grains were subjected to MW bioassay, genotyped with Diversity Array Technologies single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance level of 0.05 and 0.01, respectively, and located within or close to multiple-insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple-traits of which six were associated with resistance to both FAW and MW suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10-30kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of five of the six combined-resistance QTNs, thus, reinforcing the pleiotropy hypothesis. In addition, through In-silico co-functional network inferences, an additional 107 Network-based CGs (NbCGs), biologically connected to the 64 GbCGs, differentially expressed under biotic or abiotic stress were revealed within MIRGRs. The provided multiple-insect resistance physical map should contribute to the development of combined-insect resistance in maize.

scholarly journals Genetic Basis of Maize Resistance to Multiple Insect Pests: Integrated Genome-Wide Comparative Mapping and Candidate Gene Prioritization

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 689
Author(s):  
A. Badji ◽  
D. B. Kwemoi ◽  
L. Machida ◽  
D. Okii ◽  
N. Mwila ◽  
...  
Keyword(s):  
Insect Resistance ◽  
Defense Mechanisms ◽  
Genome Wide Association Study ◽  
Insect Pests ◽  
Physical Map ◽  
Fall Armyworm ◽  
Nucleotide Polymorphisms ◽  
Multiple Traits ◽  
Maize Weevil ◽  
Genome Wide

Several species of herbivores feed on maize in field and storage setups, making the development of multiple insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to fall armyworm (FAW), whilst bulked grains were subjected to a maize weevil (MW) bioassay and genotyped with Diversity Array Technology’s single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance levels of 0.05 and 0.01, respectively, and located within or close to multiple insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple traits, of which, six were associated with resistance to both FAW and MW, suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10–30 kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of the five of the six combined resistance QTNs, thus reinforcing the pleiotropy hypothesis. In addition, through in silico co-functional network inferences, an additional 107 network-based CGs (NbCGs), biologically connected to the 64 GbCGs, and differentially expressed under biotic or abiotic stress, were revealed within MIRGRs. The provided multiple insect resistance physical map should contribute to the development of combined insect resistance in maize.

scholarly journals Genetic Basis of Maize Resistance to Multiple-Insect Pests: Integrated Genome-Wide Comparative Mapping and Candidate Gene Prioritization

2020 ◽  
Author(s):  
Arfang Badji ◽  
Daniel Bomet Kwemoi ◽  
Lewis Machida ◽  
Dennis Okii ◽  
Natasha Mwila ◽  
...  
Keyword(s):  
Insect Resistance ◽  
Genome Wide Association Study ◽  
Insect Pests ◽  
Physical Map ◽  
Fall Armyworm ◽  
Nucleotide Polymorphisms ◽  
Multiple Traits ◽  
Maize Weevil ◽  
Significance Level ◽  
Genome Wide

Several herbivores feed on maize in field and storage setups making the development of multiple-insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to FAW (fall armyworm) whilst bulked grains were subjected to MW (maize weevil) bioassay, genotyped with Diversity Array Technologies single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance level of 0.05 and 0.01, respectively, and located within or close to multiple-insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple-traits of which six were associated with resistance to both FAW and MW suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10-30kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of five of the six combined-resistance QTNs, thus, reinforcing the pleiotropy hypothesis. In addition, through In-silico co-functional network inferences, an additional 107 Network-based CGs (NbCGs), biologically connected to the 64 GbCGs, differentially expressed under biotic or abiotic stress were revealed within MIRGRs. The provided multiple-insect resistance physical map should contribute to the development of combined-insect resistance in maize.

scholarly journals Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

2015 ◽  
Vol 75 (4) ◽  
pp. 652-659 ◽  
Author(s):  
Hirotaka Matsuo ◽  
Ken Yamamoto ◽  
Hirofumi Nakaoka ◽  
Akiyoshi Nakayama ◽  
Masayuki Sakiyama ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Clinical Information ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Clinical Parameters ◽  
Nucleotide Polymorphisms ◽  
Male Population ◽  
Significance Level ◽  
Genome Wide

ObjectiveGout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only.MethodsA GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls.ResultsFive gout susceptibility loci were identified at the genome-wide significance level (p<5.0×10−8), which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10−12; OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10−23; OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10−9; OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case–control ORs for two distinct types of gout (r=0.96 [p=4.8×10−4] for urate clearance and r=0.96 [p=5.0×10−4] for urinary urate excretion).ConclusionsOur findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics.

scholarly journals Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent

2020 ◽  
Author(s):  
Ken Batai ◽  
Mario J Trejo ◽  
Yuliang Chen ◽  
Lindsay N Kohler ◽  
Peter Lance ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
European Descent ◽  
Significance Level ◽  
Genome Wide ◽  
A Genome ◽  
Basal Plasma

ABSTRACT Background Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. Objectives A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. Methods A total of 428 participants aged 40–80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. Results No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10−7), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10−8). Conclusions This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants

2019 ◽  
Vol 36 (14) ◽  
pp. 1453-1458 ◽  
Author(s):  
Ariana M. Spiegel ◽  
Jingjing Li ◽  
John W. Oehlert ◽  
Jonathan A. Mayo ◽  
Cecele C. Quaintance ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Genome Wide Association Study ◽  
Periventricular Leukomalacia ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Very Preterm Infants ◽  
Significance Level ◽  
Very Preterm ◽  
Genome Wide ◽  
A Genome

Objective To identify single nucleotide polymorphisms (SNPs) associated with clinical chorioamnionitis among preterm infants. Study Design We reanalyzed a genome-wide association study (GWAS) from preterm newborns at less than 30 weeks' gestation. Cases and control definitions were determined using administrative records. There were 213 clinical chorioamnionitis cases and 707 clinically uninfected controls. We compared demographic and clinical outcomes of cases and controls. We performed a GWAS and compared the distribution of SNPs from the background genes and from the immunome genes. We used a Wilcoxon's rank-sum test to compare the SNPs normalized odds ratio and used odds ratios and p-values to determine candidate genes. Results Infants affected by clinical chorioamnionitis were more likely to have periventricular leukomalacia, high-grade retinopathy, and high-grade intraventricular hemorrhage (IVH). Although a GWAS did not identify SNPs associated with clinical chorioamnionitis at the genome-wide significance level, a direct test on the exonic variants in the human immunome revealed their significant increase of risk in clinical chorioamnionitis. Conclusion Among very preterm infants, clinical chorioamnionitis was associated with periventricular leukomalacia, high-grade retinopathy, and IVH. Our analysis of variants in the human immunome indicates an association with clinical chorioamnionitis in very preterm pregnancies.

scholarly journals GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

2016 ◽  
Vol 76 (5) ◽  
pp. 869-877 ◽  
Author(s):  
Akiyoshi Nakayama ◽  
Hirofumi Nakaoka ◽  
Ken Yamamoto ◽  
Masayuki Sakiyama ◽  
Amara Shaukat ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Human Kidney ◽  
Nucleotide Polymorphisms ◽  
Susceptibility Loci ◽  
Significance Level ◽  
Urate Transporter ◽  
Genome Wide ◽  
A Genome ◽  
Novel Concept

ObjectiveA genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific.MethodsPutative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study.ResultsIn addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10−8): urate transporter genes (SLC22A12andSLC17A1) andHIST1H2BF-HIST1H4Efor all gout cases, andNIPAL1andFAM35Afor the renal underexcretion gout subtype. WhileNIPAL1encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, andFAM35Awas associated with gout in all cases. A meta-analysis of the three populations revealedFAM35Ato be associated with gout at a genome-wide level of significance (pmeta=3.58×10−8).ConclusionsOur findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia.

Genome-wide association study identifies novel susceptibility loci for migraine in Han Chinese resided in Taiwan

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 466-475 ◽  
Author(s):  
Shih-Pin Chen ◽  
Jong-Ling Fuh ◽  
Ming-Yi Chung ◽  
Ying-Chao Lin ◽  
Yi-Chu Liao ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Positive Association ◽  
Susceptibility Genes ◽  
Han Chinese ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Significance Level ◽  
Genome Wide

Background Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10−4 in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom. Variants at LRP1, TRPM8, and PRDM, which have been replicated in Caucasians, were also genotyped. Results We identified a novel susceptibility locus (rs655484 in DLG2) that reached GWAS significance level for migraine risk in Han Chinese ( p = 1.45 × 10−12, odds ratio [OR] = 2.42), and also another locus (rs3781545in GFRA1) with suggestive significance ( p = 1.27 × 10−7, OR = 1.38). In addition, we observed positive association signals with a similar trend to the associations identified in Caucasian GWASs for rs10166942 in TRPM8 (OR = 1.33, 95% confidence interval [CI] = 1.14–1.54, Ppermutation = 9.99 × 10−5; risk allele: T) and rs1172113 in LRP1 (OR = 1.23, 95% CI = 1.04–1.45, Ppermutation = 2.9 × 10−2; risk allele: T). Conclusion The present study is the first migraine GWAS conducted in Han-Chinese and Asians. The newly identified susceptibility genes have potential implications in migraine pathogenesis. DLG2 is involved in glutamatergic neurotransmission, and GFRA1 encodes GDNF receptors that are abundant in CGRP-containing trigeminal neurons. Furthermore, positive association signals for TRPM8 and LRP1 suggest the possibility for common genetic contributions across ethnicities.

scholarly journals Graves’ Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Dide Wu ◽  
Wei Xian ◽  
Shubin Hong ◽  
Boyuan Liu ◽  
Haipeng Xiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Statistical Power ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Asian Population ◽  
Graves Disease ◽  
Nucleotide Polymorphisms ◽  
Significance Level ◽  
Genome Wide ◽  
A Genome

BackgroundThe frequent coexistence of Graves’ disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases.MethodsWe retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P &lt; 5.0 × 10−8). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion’s method.ResultsOur study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10–1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94–1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa.ConclusionsWe found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.

scholarly journals Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jianhua Chen ◽  
Ping Yang ◽  
Qian Zhang ◽  
Ruirui Chen ◽  
Peng Wang ◽  
...  
Keyword(s):  
Association Study ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Significance Level ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

Abstract Background Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). Methods A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). Results The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10−8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10−8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. Conclusions The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.

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 &lt; 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.

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