Variance-quantitative trait loci enable systematic discovery of gene-environment interactions for cardiometabolic serum biomarkers

Gene-environment interactions (GEIs) represent the modification of genetic effects by environmental exposures and are critical for understanding disease and informing personalized medicine. GEIs often induce differential phenotypic variance across genotypes; these variance-quantitative trait loci (vQTLs) can be prioritized in a two-stage GEI detection strategy to greatly reduce the computational and statistical burden and enable testing of a broader range of exposures. We performed genome-wide vQTL analysis for 20 serum cardiometabolic biomarkers by multi-ancestry meta-analysis of 350,016 unrelated participants in the UK Biobank, identifying 182 independent locus-biomarker pairs (p < 4.5x10-9). Most vQTLs were concentrated in a small subset (4%) of loci with genome-wide significant main effects, and 44% replicated (p < 0.05) in the Women's Genome Health Study (N = 23,294). Next, we tested each vQTL for interaction across 2,380 exposures, identifying 846 significant GEIs (p < 2.4x10-7). Specific examples demonstrated interaction of triglyceride-associated variants with distinct body mass- versus body fat-related exposures as well as genotype-specific associations between alcohol consumption and liver stress at the ADH1B gene. Our catalog of vQTLs and GEIs is publicly available in an online portal.

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Meta-Analysis of Quantitative Trait Loci Associated with Seedling-Stage Salt Tolerance in Rice (Oryza sativa L.)

Plants ◽

10.3390/plants8020033 ◽

2019 ◽

Vol 8 (2) ◽

pp. 33 ◽

Cited By ~ 6

Author(s):

Md. Islam ◽

John Ontoy ◽

Prasanta Subudhi

Keyword(s):

Quantitative Trait Loci ◽

Salt Tolerance ◽

Candidate Genes ◽

Quantitative Trait ◽

Oryza Sativa L ◽

Meta Analysis ◽

Seedling Stage ◽

Phenotypic Variance ◽

A Genome ◽

Trait Loci

Soil and water salinity is one of the major abiotic stresses that reduce growth and productivity in major food crops including rice. The lack of congruence of salt tolerance quantitative trait loci (QTLs) in multiple genetic backgrounds and multiple environments is a major hindrance for undertaking marker-assisted selection (MAS). A genome-wide meta-analysis of QTLs controlling seedling-stage salt tolerance was conducted in rice using QTL information from 12 studies. Using a consensus map, 11 meta-QTLs for three traits with smaller confidence intervals were localized on chromosomes 1 and 2. The phenotypic variance of 3 meta-QTLs was ≥20%. Based on phenotyping of 56 diverse genotypes and breeding lines, six salt-tolerant genotypes (Bharathy, I Kung Ban 4-2 Mutant, Langmanbi, Fatehpur 3, CT-329, and IARI 5823) were identified. The perusal of the meta-QTL regions revealed several candidate genes associated with salt-tolerance attributes. The lack of association between meta-QTL linked markers and the level of salt tolerance could be due to the low resolution of meta-QTL regions and the genetic complexity of salt tolerance. The meta-QTLs identified in this study will be useful not only for MAS and pyramiding, but will also accelerate the fine mapping and cloning of candidate genes associated with salt-tolerance mechanisms in rice.

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Detection of quantitative trait loci for resistance/susceptibility to pseudorabies virus in swine

Journal of General Virology ◽

10.1099/0022-1317-83-1-167 ◽

2002 ◽

Vol 83 (1) ◽

pp. 167-172 ◽

Cited By ~ 39

Author(s):

Gerald Reiner ◽

Elke Melchinger ◽

Marcela Kramarova ◽

Eberhardt Pfaff ◽

Matthias Büttner ◽

...

Keyword(s):

Quantitative Trait Loci ◽

Quantitative Trait ◽

Pseudorabies Virus ◽

Neurological Symptoms ◽

Pseudoautosomal Region ◽

Phenotypic Variance ◽

Large White ◽

Genome Wide ◽

A Genome ◽

Trait Loci

This study describes genetic differences in resistance/susceptibility to pseudorabies virus (PrV) between European Large White and Chinese Meishan pigs, with a mapping of quantitative trait loci (QTL) obtained from a genome-wide scan in F2 animals. Eighty-nine F2 pigs were challenged intranasally at 12 weeks with 105 p.f.u. of the wild-type PrV strain NIA-3. For QTL analysis, 85 microsatellite markers, evenly spaced on the 18 porcine autosomes and on the pseudoautosomal region of the X chromosome, were genotyped. All pigs developed clinical signs, i.e. fever, from 3 to 7 days p.i. The pure-bred Large White pigs, the F1 and three-quarters of the F2 animals, but none of the Meishan pigs, developed neurological symptoms and died or were euthanized. QTLs for appearance/non-appearance of neurological symptoms were found on chromosomes 9, 5, 6 and 13. They explained 10·6–17·9% of F2 phenotypic variance. QTL effects for rectal temperature after PrV challenge were found on chromosomes 2, 4, 8, 10, 11 and 16. Effects on chromosomes 9, 10 and 11 were significant on a genome-wide level. The results present chromosomal regions that are associated with presence/absence of neurological symptoms as well as temperature course after intranasal challenge with NIA-3. The QTLs are in proximity to important candidate genes that are assumed to play crucial roles in host defence against PrV.

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Genome-wide association studies and meta-analysis reveal novel quantitative trait loci and pleiotropic loci for swine head-related traits

Journal of Animal Science ◽

10.2527/jas2016.1137 ◽

2017 ◽

Vol 95 (6) ◽

pp. 2354

Author(s):

H. Chen ◽

T. Huang ◽

Z. Zhang ◽

B. Yang ◽

C. Jiang ◽

...

Keyword(s):

Quantitative Trait Loci ◽

Quantitative Trait ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Trait Loci

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Genome-wide association studies and meta-analysis reveal novel quantitative trait loci and pleiotropic loci for swine head-related traits1,2

Journal of Animal Science ◽

10.2527/jas.2016.1137 ◽

2017 ◽

Vol 95 (6) ◽

pp. 2354-2366

Author(s):

H. Chen ◽

T. Huang ◽

Z. Zhang ◽

B. Yang ◽

C. Jiang ◽

...

Keyword(s):

Quantitative Trait Loci ◽

Quantitative Trait ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Trait Loci

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Quantitative Trait Loci: A Meta-analysis

Genetics ◽

10.1093/genetics/155.1.463 ◽

2000 ◽

Vol 155 (1) ◽

pp. 463-473

Author(s):

Bruno Goffinet ◽

Sophie Gerber

Keyword(s):

Quantitative Trait Loci ◽

Confidence Interval ◽

Quantitative Trait ◽

Meta Analysis ◽

Trait Loci ◽

Akaike Criterion ◽

Using Data

Abstract This article presents a method to combine QTL results from different independent analyses. This method provides a modified Akaike criterion that can be used to decide how many QTL are actually represented by the QTL detected in different experiments. This criterion is computed to choose between models with one, two, three, etc., QTL. Simulations are carried out to investigate the quality of the model obtained with this method in various situations. It appears that the method allows the length of the confidence interval of QTL location to be consistently reduced when there are only very few “actual” QTL locations. An application of the method is given using data from the maize database available online at http://www.agron.missouri.edu/.

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Quantitative Trait Loci for Susceptibility to Tapeworm Infection in the Red Flour Beetle

Genetics ◽

10.1093/genetics/165.3.1307 ◽

2003 ◽

Vol 165 (3) ◽

pp. 1307-1315

Author(s):

Daibin Zhong ◽

Aditi Pai ◽

Guiyun Yan

Keyword(s):

Quantitative Trait Loci ◽

Quantitative Trait ◽

Genetic Basis ◽

Life Cycles ◽

Red Flour Beetle ◽

Phenotypic Variance ◽

Flour Beetle ◽

Trait Loci ◽

Host Ecology ◽

Tapeworm Infection

Abstract Parasites have profound effects on host ecology and evolution, and the effects of parasites on host ecology are often influenced by the magnitude of host susceptibility to parasites. Many parasites have complex life cycles that require intermediate hosts for their transmission, but little is known about the genetic basis of the intermediate host's susceptibility to these parasites. This study examined the genetic basis of susceptibility to a tapeworm (Hymenolepis diminuta) in the red flour beetle (Tribolium castaneum) that serves as an intermediate host in its transmission. Quantitative trait loci (QTL) mapping experiments were conducted with two independent segregating populations using amplified fragment length polymorphism (AFLP) markers and randomly amplified polymorphic DNA (RAPD) markers. A total of five QTL that significantly affected beetle susceptibility were identified in the two reciprocal crosses. Two common QTL on linkage groups 3 and 6 were identified in both crosses with similar effects on the phenotype, and three QTL were unique to each cross. In one cross, the three main QTL accounted for 29% of the total phenotypic variance and digenic epistasis explained 39% of the variance. In the second cross, the four main QTL explained 62% of the variance and digenic epistasis accounted for only 5% of the variance. The actions of these QTL were either overdominance or underdominance. Our results suggest that the polygenic nature of beetle susceptibility to the parasites and epistasis are important genetic mechanisms for the maintenance of variation within or among beetle strains in susceptibility to tapeworm infection.

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The Genetic Basis of the Interspecific Differences in Wing Size in Nasonia (Hymenoptera; Pteromalidae): Major Quantitative Trait Loci and Epistasis

Genetics ◽

10.1093/genetics/161.2.673 ◽

2002 ◽

Vol 161 (2) ◽

pp. 673-684

Author(s):

J Gadau ◽

R E Page ◽

J H Werren

Keyword(s):

Quantitative Trait Loci ◽

Qtl Analysis ◽

Quantitative Trait ◽

Wing Length ◽

Size Difference ◽

Phenotypic Variance ◽

Wing Size ◽

Epistatic Interactions ◽

Trait Loci ◽

Wing Width

Abstract There is a 2.5-fold difference in male wing size between two haplodiploid insect species, Nasonia vitripennis and N. giraulti. The haploidy of males facilitated a full genomic screen for quantitative trait loci (QTL) affecting wing size and the detection of epistatic interactions. A QTL analysis of the interspecific wing-size difference revealed QTL with major effects and epistatic interactions among loci affecting the trait. We analyzed 178 hybrid males and initially found two major QTL for wing length, one for wing width, three for a normalized wing-size variable, and five for wing seta density. One QTL for wing width explains 38.1% of the phenotypic variance, and the same QTL explains 22% of the phenotypic variance in normalized wing size. This corresponds to a region previously introgressed from N. giraulti into N. vitripennis that accounts for 44% of the normalized wing-size difference between the species. Significant epistatic interactions were also found that affect wing size and density of setae on the wing. Screening for pairwise epistatic interactions between loci on different linkage groups revealed four additional loci for wing length and four loci for normalized wing size that were not detected in the original QTL analysis. We propose that the evolution of smaller wings in N. vitripennis males is primarily the result of major mutations at few genomic regions and involves epistatic interactions among some loci.

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Quantitative Trait Loci Affecting Differences in Floral Morphology Between Two Species of Monkeyflower (Mimulus)

Genetics ◽

10.1093/genetics/149.1.367 ◽

1998 ◽

Vol 149 (1) ◽

pp. 367-382 ◽

Cited By ~ 11

Author(s):

H D Bradshaw ◽

Kevin G Otto ◽

Barbara E Frewen ◽

John K McKay ◽

Douglas W Schemske

Keyword(s):

Quantitative Trait Loci ◽

Reproductive Isolation ◽

Quantitative Trait ◽

Floral Morphology ◽

Cumulative Effect ◽

Sympatric Species ◽

Accurate Estimate ◽

Phenotypic Variance ◽

Trait Loci ◽

Morphological Differences

Abstract Conspicuous differences in floral morphology are partly responsible for reproductive isolation between two sympatric species of monkeyflower because of their effect on visitation of the flowers by different pollinators. Mimulus lewisii flowers are visited primarily by bumblebees, whereas M. cardinalis flowers are visited mostly by hummingbirds. The genetic control of 12 morphological differences between the flowers of M. lewisii and M. cardinalis was explored in a large linkage mapping population of F2 plants (n = 465) to provide an accurate estimate of the number and magnitude of effect of quantitative trait loci (QTLs) governing each character. Between one and six QTLs were identified for each trait. Most (9/12) traits appear to be controlled in part by at least one major QTL explaining ≥25% of the total phenotypic variance. This implies that either single genes of individually large effect or linked clusters of genes with a large cumulative effect can play a role in the evolution of reproductive isolation and speciation.

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