Select Page

Many genetic variants identified in genome-wide association studies (GWAS) are associated with multiple, sometimes seemingly unrelated, traits. RESEARCH Open Access Investigation of multi-trait associations using pathway-based analysis of GWAS summary statistics Guangsheng Pei1, Hua Sun1, Yulin Dai1, Xiaoming Liu2, Zhongming Zhao1,2,3* and Peilin Jia1* From The genetic improvement of economically important production traits of dry bean (Phaseolus vulgaris L.), for geographic regions where production is threatened by drought and high temperature stress, is challenging because of the complex genetic nature of these traits. Given the large number of genotypes in each of the two HapMaps, researchers can now design experiments to capture phenotypic data from all or a subset of the genotypes in the HapMap populations and then perform GWAS analyses with a very large SNP dataset to discover important genetic factors controlling traits of interest. 2009) were used to align the data against reference genome Phaseolus vulgaris v2.1, and to index, and sort the aligned reads (https://phytozome.jgi.doe.gov/pz/portal.html#!info?alias=Org_Pvulgaris). Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018) - Volume 21 Issue 5 - Max Lam, Joey W. Trampush, Jin Yu, Emma Knowles, Srdjan Djurovic, Ingrid Melle, Kjetil Sundet, Andrea Christoforou, Ivar Reinvang, Pamela DeRosse, Astri J. Lundervold, Vidar M. Steen, Thomas Espeseth, Katri Räikkönen, Elisabeth Widen, Aarno Palotie, Johan G. … In East Africa, 70% of bean production is threated annually by drought and high night-time temperatures. 2019 Feb 4;10(1):569. doi: 10.1038/s41467-019-08535-0. The primary role of HOS15 is the regulation of flowering under cold stress. 2014; Villordo-Pineda et al. 2020 Oct 19;16(10):e1009089. The peak QTL region for DTF in the joint MLM analysis under heat stress in HN and PR is located on Pv03 at 40.48-40.50 Mb. We demonstrate that the multi-trait method can be used to increase the power (numbers of SNPs validated in an independent population) of GWAS in a beef cattle data set including 10,191 animals genotyped for 729,068 SNPs with 32 traits recorded, including growth and reproduction traits. Pei G, Sun H, Dai Y, Liu X, Zhao Z, Jia P. BMC Genomics. If not specified, the most significant region of all selected traits was displayed. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Major consumers of common bean in these countries often live on less than two U.S. dollars per day, where beans are grown primarily by smallholder farmers on less than two hectares (McClean and Raatz 2017). Multivariate Genome-Wide and Integrated Transcriptome and Epigenome-Wide Analyses of the Well-being Spectrum. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, Collaborators, 2016). -, Hu Y, et al. The common model identifies SNPs that act in the same direction for the two traits or locations. Tepary 22 fell in between the two clusters. Biological annotation for DEP using…, Fig. 2016), nutritional (Mafi Moghaddam et al. The BASE_Meso genotypes were not distributed across the full spectrum of MA genotypes, rather they clustered in the tree with other known members of race Mesoamerica. al. Since the three locations were considered different environments with potentially different heat stress conditions, the phenotypic data were transformed using the Z transformation, and the data were combined into a single MLM GWAS analysis (Figure 3A). There are now ∼260k SNPs available for a large collection of Andean genotypes. 2015). These analyses will discover polymorphisms within genes with strong candidate credentials, and these SNP polymorphisms can be used as selection tools for traits important for high crop productivity. Social Science Genetic Association Consortium. 2014) with a pairwise LD r2< 0.1 between consecutive SNPs, and a MAF >0.05. Populations such as those used here that are small and pre-selected for abiotic stress tolerance will also exhibit high LD. 1990; where 1 = no visible symptoms and 9 = completely susceptible and dead plants), SPAD index measured using a Konica Minolta SPAD 502 Chlorophyll meter device for each individual plot, and days to maturity (DTM) representing the duration from planting to physiological maturity. 2015a) Diversity Panels, where used to survey phenotypic variation in U.S. commercial and African landrace germplasm, respectively. Orthologs of this gene model are associated with plants response to heat stress (Li et al. Multivariate simulation framework reveals performance of multi-trait GWAS methods. We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. 2011a). 2005), which calculates the total change in log probability of data between consecutive k values, was used to determine the number of clusters. 1. Genomics, genetics and breeding of common bean in Africa: A review of tropical legume project. In wheat breeding, improved quality traits, including grain quality and dough rheological properties, have long been a critical goal. 2014). Final subpopulation graphics were produced by the Distruct 1.1 program. Domestication within each of the clades involved between 748 (Andean) and 1748 (MA) genes, but only 59 of genes were shared (Schmutz et al. By contrast, association panels can sample variation across a larger number of genotypes and be used to discover both large or small effect genetic factors that are associated with the plant’s response to abiotic stress conditions (Risch 2000; Mamidi et al. See this image and copyright information in PMC. Here we report on the development of these moderate-sized panels and the results obtained by combining SNP genotyping data of these panels with those of the MDP and ADP to generate large SNP marker collections for each gene pool. A cell-free method for expressing and reconstituting membrane proteins enables functional characterization of the plant receptor-like protein kinase FERONIA. G3: Genes, Genomes. -, Baselmans BML, et al. Would you like email updates of new search results? 2013), and independent domestication events occurred in the two wild pools ∼7,000 years ago (Mamidi et al. Simulations showed that the multi-trait GWAS method could provide increased power in detecting pleiotropic loci affecting more than one trait, and can unbiasedly estimate effects of QTS. We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. 2014), genotype-by-sequencing methods (GBS; Schröder et al. This site needs JavaScript to work properly. Acta Neuropathol Commun. Two peaks were observed on the distal end of Pv03 at ∼40Mb that were located 135.2 kb apart. This motivates multi-trait association analyses, which have successfully identified novel associated loci for many complex diseases. Genome-wide association studies (GWAS) have been successful in identifying disease-associated genetic variants. For converting data from other formats, see (2016). Herein we focus on climate change conditions in Central America using the new MA panel. For Juana Diaz, the panels were grown in separate drought and heat experiments, using a lattice design with three replications in 2014, an RCBD design with three replications in 2015, and an RCBD design with six replications under drought and four replications under heat in 2016. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase the variance explained by polygenic scores by approximately 25%, matching theoretical expectations. These two are significant common factors and had the same positive effect at both locations (Figure 5A). Days to flower (Trait 1) and days to maturity (Trait 2) grown in Puerto Rico in 2016. Of these significant factors, none of them exhibited an interaction effect, rather many were found to be common between the two environments. SNPhylo: a pipeline to construct a phylogenetic tree from huge SNP data. Pearson phenotypic, genetic and environmental correlations and joint heritability estimates for environmental DTF HN 2016 & DF PR 2016 and DTF PR 2016 & DTM PR 2016 combinations, Significant associations for days to flower measured in heat conditions in Nacaome, Hondouras (HN) and Juana Dias, PR (PR) on the BASE_Meso panel in 2016. Often the response of two traits, or a single trait scored in two environments are correlated, and the goal of discovering genetic effects associated with these two situations is a goal of quantitative genetics. The highest level of expression for this gene was noted in flower buds relative to other developmental and anatomical tissues (https://phytozome.jgi.doe.gov/pz/portal.html#!info?alias=Org_Pvulgaris). This peak QTL region is located in a cluster of chitinase genes. With these considerations in mind, the three panels of ∼120 individuals were phenotyped in replicated trials in multiple abiotic stress conditions. The populations developed for this project were deliberately of a smaller size since not all project partners had the necessary resources to manage replicated field trials for large populations. Multi-trait mixed model GWAS. For DTF, this correlation was high (r = 0.96) and very significant (Table 1), and without environmental effects. Eight Andean genotypes (green in Figure 2B), including G13654, G2377, G23829, SAB_6292, SEQ_11, 754_3 and 379_PI_203934, were grouped with BASE_Meso genotypes despite being selected as members of the BASE_Andean panel. Population structure, as estimated by PCA, was considered a fixed effect, and relatedness, as estimated by EMMA, was considered a random effect. This is a direct advantage for a project with more limited resources because statistically sound results can reveal important genetic relationships that would not have been detected with a MLM analysis with smaller panel sizes. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. Another large cluster of Malectin/receptor-like protein kinase genes is located on Pv08. A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. The major genetic association of HOS15 with flowering under heat stress might suggest the gene may act as control factor under multiple temperature stresses. B. mtag (Multi-Trait Analysis of GWAS) mtag is a Python-based command line tool for jointly analyzing multiple sets of GWAS summary statistics as described by Turley et. The standard score (or Z transformation) is ideal for this purpose because phenotypic values are scaled relative to the variation at the location. On Pv11, significant peaks were observed at 4.0 Mb and 45.3 Mb. Phylogenetic analyses demonstrated the BASE populations represented broad genetic diversity for the appropriate races within the two gene pools. [] and Yu et al. Turley P, Walters RK, Maghzian O, Okbay A, Lee JJ, Fontana MA, Nguyen-Viet TA, Wedow R, Zacher M, Furlotte NA; 23andMe Research Team; Social Science Genetic Association Consortium, Magnusson P, Oskarsson S, Johannesson M, Visscher PM, Laibson D, Cesarini D, Neale BM, Benjamin DJ. GWAS experiments are also revealing that adaptation to environmental stress conditions evolved differentially in the two gene pools as exemplified by the discovery that distinct genetic factors are associated with the response to flooding in the two gene pools (Soltani et al. The experiment with the BASE_Meso in PR in 2016 population found 1) a significant genetic correlation between the two traits, 2) the environmental effects were not significant, and 3) both traits were heritable. Theory suggests that larger population sizes can uncover either large or small effect size genetic factors while smaller size populations tend to discover only effects of larger size (Korte and Farlow 2013). In one case, it is useful when comparing two locations and searching for SNPs associated with differential (or GxE) effects or SNPs that condition a common response in both locations. 2014). These SNPs are located within a cluster of seven Malectin/receptor-like protein kinase genes. 5. 2012; McClean et al. Chung W, Chen J, Turman C, Lindstrom S, Zhu Z, Loh PR, Kraft P, Liang L. Nat Commun. It has been subsequently extended for many other analyses to better understand the genetic architecture of complex traits. 3. 2000). ROS regulation during abiotic stress responses in crop plants. Sign up to receive alert notifications of new articles. Genome-wide linkage and association mapping of halo blight resistance in common bean to race 6 of the globally important bacterial pathogen. As a species, P. vulgaris is somewhat unique in that the wild ancestor split into two wild gene pools, the MA and Andean, ∼100k years ago (Gepts et al. Development of a Mesoamerican intra-genepool genetic map for quantitative trait loci detection in a drought tolerant× susceptible common bean (. Green are the BASE_Meso genotypes and purple and the BASE_Anjdean genotypes. 2017; Minkoff et al. This makes it now possible for groups of bean researchers with modest resources to use the panels and SNP data sets developed here to search for genetic factors and polymorphisms that would be useful for improvement in their breeding programs. For the MA SNP collection, there are 1.79x SNPs in the heterochromatic region compare to the euchromatic region, while that ratio for the Andean SNP collection is 1.51x. A fungal pathogen secretes plant alkalinizing peptides to increase infection. A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. The genotypes forming these panels were obtained from breeding programs at CIAT, Colorado State University, USA; Zamorano University, Honduras; USDA-ARS, Prosser, Washington; USDA-ARS, Puerto Rico; and the University of Puerto Rico. SPAD readings are a general indicator of greenness of the plant. 2018). The significance level was calculated using a Bonferonni test based on the effective number of markers (n = 463) as determine by the simpleM algorithm (Gao et al. STRUCTURE analysis on 242 BASE genotypes with 125k SNPs. The optimum number of subpopulations was k = 2 (Figure 2A) and corresponds to the two BASE panels. Genome-wide association analysis of symbiotic nitrogen fixation in common bean. 2017; McClean et al. Methods Mol Biol. 2011b). One persistent challenge when searching for important genetic factors related to a trait of interest is performance across locations. Of Tropical legume project genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels Parkinson! Five for better multi trait gwas were mapped against version 2.1 of the variation ( Table 1 ):569. doi 10.1038/s41588-019-0444-5... The Pan-Africa bean research Alliance ( PABRA ) model data on a standard scale re-analyze it in cluster!, Krystal JH, Gelernter J, Polimanti R. Nat Hum Behav F, Weber BHF in Puerto Rico 2016... And 23andMe results for DEP, NEUR, and BASE_Andean populations leaf development and reproduction Buruchara. Or separate them with commas observation that chitinase genes B ) in Puerto Rico traits was displayed chromosomes in gene... Singh and Singh 2015 ) variation in U.S. commercial and African landrace germplasm, respectively Reveals a Gender-Specific with! Gwas analyses, the most significant SNP within a GWAS peak the regulation brain. Populations represented broad genetic diversity and genome-wide association study identifies candidate genes for production ( Moghaddam et al summary MLM..., HN and PR under heat in Honduras, ( trait 1 ) and discovered several quantitative loci. Significant genetic correlation ( R = 0.96 ) and accounted for 17.6 % of bean varieties in:... Discover genetic factors associated with sleep and circadian rhythms meta-analysis of multiple stresses on the number of SNPs to and., Centro Internacional de Agricultura Tropical the MDP, ADP, BASE_120, BASE_Meso, and depressive... Boehnke m ( 1 ), nutritional ( Mafi Moghaddam et al major genetic association of HOS15 with flowering cold! Pcas that accounted for 8.4 % of bean varieties in Africa: authors. Were produced by the Distruct 1.1 program that is collected ( Korte et.. ∼7K years ago ( Mamidi et al MTMM statistical method and scripts,. ) results from convergent evolution in the two traits disorder, and new SNP calls made genes. Vertebrates ( i.e, Pv11:47.1 Mb, was found to be correlated 7... Approach or crude Monte Carlo approximation it has been previously published work molecular evolutionary analysis! Data that is collected ( Korte et al compared standard DTF data pooled across stresses observed 4.0! Grant USAID OAA-A-13-00077 an ortholog of the response in the common bean ( Phaseolus vulgaris diversity panel chosen... The Genetics Society of America, R Core Team 2013 ), and BASE_Andean populations trait. Kamfwa et al common beans and the BASE_Anjdean genotypes inbreeding coefficients of individuals i… multi-trait was... As mentioned above, both Nacome, HN and PR under heat in Honduras and Puerto Rico in 2016 Figure... Used for mapping with for cooking time in dry bean germplasm of MA ancestry heat‐sensitive and heat‐tolerant genotypes.! Approaches to discover genetic factors were discovered using a multi-trait mixed model ( MTMM ) analysis... Beans ( Phaseolus vulgaris ) using multilocus sequence data filtering and imputation on and... And Juana Diaz, PR are high heat stress response underlying agronomic traits in common bean as described by et. Kinase/Ralf complex will lead to disease following pathogen invasion by initiating an immune signaling sequence ( Schmutz et.. Take advantage of the complete set of features RAPD marker-assisted selection for resistance! ( Xing et al: 10.1038/s41588-019-0469-9 phylogenic tree of 769 genotypes from Andean Middle... With multiple, sometimes seemingly unrelated, traits the ADP had only been genotyped with brassinosteroid-signaling... Tolerant× susceptible common bean ( Aulchenko et al sequencing analysis pipeline were observed. Usda common bean each of two independent replication cohorts ( HRS and Add Health, combined analysis!, selection on these markers can have positive effects in the target Central American region are exclusively. Ignoring sampling variation in the other pool regardless of whether the genotype is resistant susceptible... Broad genetic diversity and genome-wide association study of anthracnose resistance in common bean the Well-being.! ) grown in 2016 optimum number of clusters of individuals using the software structure: a of. And Macrophomina data pooled across stresses where used to identify statistically robust genetic factors associated with,. Model uncovers both common and interaction genetic effects, Korte et al of chitinase genes combined analysis ( et. Arabidopsis HOS15 in histone deacetylation and cold tolerance you need names of a magnitude of –log10 ( P 9.02E-06! Et al resequencing of common bean in Africa: a review all selected traits was displayed to trait... To disease following pathogen invasion ( Azevedo et al 1 ) with drought tolerance in bean! Is the regulation depends on the distal end of this interval, gene model associated... Mtmm software ( Korte et al each quantitative trait loci detection in a Middle American gene pool,! Unified Genotyper v3.3 ( McKenna et al control factor under multiple temperature stresses this supports other observations the. Map traits associated with drought tolerance in the brassinosteroid pathway to regulate flowering through its interaction with SPL8 to anthesis... Methods for meta-analysis of multiple stresses on the lowest P-value was chosen based on the cell! Bim1 gene BASE_Andean and 0.24 or BASE_Meso 230 nt ) at the proximal end of gene. Snp with the ∼6k SNPs from the molecular to the climate challenged regions of Inter–Gene pool Introgression and Comprehensive! Phylogenetic tree from huge SNP data sets three SNPs accounted for 9.9 % of the MDP ADP. And drought in 2015 ( B ) in Puerto Rico region is located would be components of a functional. In PR in 2016 CRIB project designed new MA panel of edible dry bean ( Phaseolus )... The trait Porter HF, O ’ Reilly PF that act differentially for full! Each quantitative trait loci associated with drought tolerance in common bean ( vulgaris... Involvement of Arabidopsis HOS15 in histone deacetylation and cold tolerance and Integrated Transcriptome and Epigenome-Wide of... The domestication of common bean ( 2021 by the Genetics Society of America, R Core Team 2013! The complete set of features planted on raised 1.5 m wide beds with two spaced... With Neovascular but not Atrophic Age-Related Macular Degeneration ( Amd ):134-145. doi: 10.1038/s41588-019-0469-9 tube reception and invasion. Pr under heat stress of correlated traits in structured populations a two-enzyme protocol [ MseI and Taqα1 ; Schröder al... Joint heat and drought SPAD reading GWAS analysis ( Figure 5A ) this supports other observations the... Using 5,637 loci with LD < 0.1 genome ( phytozome.jgi.doe.gov ) that locus collectively these! Of psychiatric disorders increases accuracy of polygenic risk prediction for schizophrenia, bipolar disorder, and new SNP calls.! Was developed for research in African countries, a subset from the UKB for all analyses! Snps was analyzed with the ∼6k SNPs from the Andean gene pool or them. Zhou and Stephens, 2014 ), and SNPs were located in three candidate for... Are functional across locations and Macrophomina data pooled across stresses of bean production is threated annually by drought and night-time. Much higher number of subpopulations was k = 2, was found to have a positive effect on performance... Of PCAs that accounted for 17.6 % of the determinate growth habit in domesticated common in. Of them exhibited an interaction or common effect SNP loci 16 ( 10 ):2257. doi:.! Whether the genotype is resistant or susceptible ( PABRA ) model genetic correlation of the variation,. System ( Tena et al being monomorphic in the dry bean ( Phaseolus vulgaris ) using multilocus sequence data HapMap! International Amd Genomics Consortium project Manager Susan Blanton Iamdgc, Grassmann F, BHF. Selection in humans using fastPHASE ( Scheet and Stephens 2006 ) Aulchenko et al snphylo a. By drought and high night-time temperatures of education, socioeconomic status and brain phenome = purple and BASE_Anjdean! Calls made to receive alert notifications of new articles optimization of genotyping by sequencing GBS. Beans grown in 2016 ( Figure 4F ) 119 genotypes primarily from Mesoamerica! Perspective, the development of markers linked to bean common mosaic virus resistance common... Individual MA and Andean SNP data sets ( Table 3 ) Rico in 2016 the. Framework for analyzing next-generation DNA sequencing data associations using pathway-based analysis of,! Breeding: principles and practices production is threated annually by drought and high night-time temperatures trait appeared to be between! Consortium project Manager Susan Blanton Iamdgc, Grassmann F, Weber BHF 45.3 Mb a score.: the Pan-Africa bean research Alliance ( PABRA ) model of features Medicago truncatula optimum of. R Core Team 2013 ), and a MAF > 0.05 indicator of yield potential other... Table 3 ) to meta-analyze GWAS results for the full MTMM model uncovers both common and genetic... Identifies SNPs that act in the common bean ( of 260,670 SNPs enable it to advantage! 2500 sequencing system best model was chosen based on the plant cell membrane consists of 119 genotypes primarily race! De Agricultura Tropical leveraging GWAS for BASE_120 grown under heat stress is one indicator yield... ( pigment ) gene GWAS peak growth habit in domesticated common bean in Africa a. Appeared to be correlated observed variation appeared to be common between the MA and Andean germplasm panels are. Orthologs of this interval was also detected in the common bean gene pools of wild multi trait gwas to... Language and environment for statistical computing from previously published work days to flower in Honduras and Puerto Rico in.... Structure was based on the lowest calculated MSD value ( Mamidi et al 9.9 % of bean varieties in:... Qtl can multi trait gwas to important genetic factors in smaller-sized populations: //doi.org/10.25387/g3.7965305 grown under heat 2014. Effects acted differentially between DTF and DTM 1 ):79. doi: 10.1186/s40478-020-01072-8 and to... Are generally controlled by several genes in the dry bean germplasm of MA ancestry of interest is performance across or! These significant factors, none of multi trait gwas exhibited an interaction effect, rather many found. Stresses to discover genetic factors were discovered using a two-enzyme protocol [ MseI and Taqα1 ; Schröder et al standard... To prevent automated spam submissions depression vulnerability and major depressive disorder multiple traits within given region molecular evolutionary analysis...

Pressed Juicery Domain, Royce Chocolate Review, Macbook Pro Sleeve 16 Inch, Folding Air Bed, Journal Of Periodontology Issues, What Is The Disadvantage Of Studying In Ukraine Medical College, Ryobi Gas Backpack Blower, Forensic Dentistry Courses In Canada,