Two-Stage Procedures for the Identification of Gene × Environment and Gene × Gene Interactions in Genome-Wide Association Studies

Kooperberg, Charles; Hsu, Li

doi:10.7551/mitpress/9780262034685.003.0002

Cited by 2 publications

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“…Recent advances in association models have included explicit modelling of categorical G × E (Kooperberg, Dai, & Hsu, ; Korte et al., ; Li et al., ; Marigorta & Gibson, ; Murcray et al., ; Thomas, ; Windle, ), but to our knowledge there are no published GWAS accounting for genotype interactions with continuous environmental gradients (a reaction norm approach, cf. Jarquín et al., ; Tiezzi et al., ).…”

Section: Discussionmentioning

confidence: 99%

Coherent synthesis of genomic associations with phenotypes and home environments

Lasky

Forester

Reimherr

2017

Molecular Ecology Resources

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Local adaptation is often studied via (i) multiple common garden experiments comparing performance of genotypes in different environments and (ii) sequencing genotypes from multiple locations and characterizing geographic patterns in allele frequency.Both approaches aim to characterize the same pattern (local adaptation), yet the complementary information from each has not yet been coherently integrated. Here, we develop a genome-wide association model of genotype interactions with continuous environmental gradients (G 9 E), that is reaction norms. We present an approach to impute relative fitness, allowing us to coherently synthesize evidence from common garden and genome-environment associations. Our approach identifies loci exhibiting environmental clines where alleles are associated with higher fitness in home environments. Simulations show our approach can increase power to detect loci causing local adaptation. In a case study on Arabidopsis thaliana, most identified SNPs exhibited home allele advantage and fitness trade-offs along climate gradients, suggesting selective gradients can maintain allelic clines. SNPs exhibiting G 9 E associations with fitness were enriched in genic regions, putative partial selective sweeps and associations with an adaptive phenotype (flowering time plasticity). We discuss extensions for situations where only adaptive phenotypes other than fitness are available. Many types of data may point towards the loci underlying G 9 E and local adaptation; coherent models of diverse data provide a principled basis for synthesis.

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Section: Discussionmentioning

confidence: 99%

Coherent synthesis of genomic associations with phenotypes and home environments

Lasky

Forester

Reimherr

2017

Molecular Ecology Resources

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show abstract

“…Recent advances in association models have included explicit modeling of categorical G×E (Murcray et al 2009;Thomas 2010;Korte et al 2012;Marigorta & Gibson 2014;Li et al 2014;Kooperberg et al 2016;Windle 2016), but to our knowledge there are no published genome-wide association studies accounting for genotype interactions with 570 continuous environmental gradients (a reaction norm approach, cf. Jarquín et al 2014;Tiezzi et al 2017).…”

Section: Genotype-by-environment Interactions In Genome-wide Associatmentioning

confidence: 99%

Coherent synthesis of genomic associations with phenotypes and home environments

Lasky

Forester

Reimherr

2016

Preprint

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Local adaptation is often studied via 1) multiple common garden experiments comparing 30 performance of genotypes in different environments and 2) sequencing genotypes from multiple locations and characterizing geographic patterns in allele frequency. Both approaches aim to characterize the same pattern (local adaptation), yet the complementary information from each has not yet been coherently integrated into a modeling framework. Here, we develop a genome-wide association model of genotype 35 interactions with continuous environmental gradients (G×E), i.e. reaction norms. We employ an imputation approach to synthesize evidence from common garden and genome-environment associations, allowing us to identify loci exhibiting environmental clines where alleles are associated with higher fitness in home environments. Simulations show our approach can increase power to detect loci causing local adaptation. In a case 40 study on Arabidopsis thaliana, our approach reveals candidate genes for local adaptation based on known involvement in environmental stress response. Most identified SNPs exhibited home allele advantage and fitness tradeoffs along climate gradients, suggesting selective gradients maintain allelic clines. SNPs exhibiting G×E associations with fitness were enriched in genic regions, putative partial selective sweeps, and G×E associations 45 with an adaptive phenotype (flowering time). We discuss extensions for situations where only adaptive phenotypes other than fitness are available. Many types of data may point toward the loci underlying G×E and local adaptation; coherent models of diverse data provide a principled basis for synthesis. Adrion JR, Hahn MW, Cooper BS (2015) Revisiting classic clines in Drosophila melanogaster in the age of genomics. Trends in Genetics. Ågren J, Oakley CG, McKay JK, Lovell JT, Schemske DW (2013) Genetic mapping of 690 adaptation reveals fitness tradeoffs in Arabidopsis thaliana.

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Two-Stage Procedures for the Identification of Gene × Environment and Gene × Gene Interactions in Genome-Wide Association Studies

Cited by 2 publications

References 0 publications

Coherent synthesis of genomic associations with phenotypes and home environments

Coherent synthesis of genomic associations with phenotypes and home environments

Coherent synthesis of genomic associations with phenotypes and home environments

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