
pmid: 26854917
pmc: PMC4767558
Abstract Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance levels of one or multiple proteins. In this work we introduce a powerful strategy that integrates gene expression measurements with large-scale genome-wide association data to identify genes whose cis-regulated expression is associated to complex traits. We use a relatively small reference panel of individuals for which both genetic variation and gene expression have been measured to impute gene expression into large cohorts of individuals and identify expression-trait associations. We extend our methods to allow for indirect imputation of the expression-trait association from summary association statistics of large-scale GWAS 1-3 . We applied our approaches to expression data from blood and adipose tissue measured in ∼3,000 individuals overall. We then imputed gene expression into GWAS data from over 900,000 phenotype measurements 4-6 to identify 69 novel genes significantly associated to obesity-related traits (BMI, lipids, and height). Many of the novel genes were associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Overall our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.
Gene Expression Regulation (mesh), Netherlands Twin Register (NTR), 3102 Bioinformatics and computational biology (for-2020), 3001 Agricultural biotechnology (for-2020), 11 Medical and Health Sciences (for), Medical and Health Sciences, 3105 Genetics (for-2020), Mice, Obesity (mesh), Animals (mesh), Genetic Predisposition to Disease (mesh), Cancer, Developmental Biology (science-metrix), Humans (mesh), Generic health relevance (hrcs-hc), Mice (mesh), Biological Sciences, Bioinformatics and computational biology, Phenotype (mesh), 06 Biological Sciences (for), Phenotype, Genome-Wide Association Study (mesh), Quantitative Trait Loci (mesh), 570, Genotype, Agricultural biotechnology, Quantitative Trait Loci, 610, SDG 3 - Good Health and Well-being, Genetics, Animals, Humans, Genetic Predisposition to Disease, Obesity, Obesity (rcdc), 31 Biological Sciences (for-2020), Genetics (rcdc), Genotype (mesh), Human Genome, Cancer (hrcs-hc), ta3121, Transcriptome (mesh), Human Genome (rcdc), Gene Expression Regulation, Generic health relevance, Transcriptome, Developmental Biology, Genome-Wide Association Study
Gene Expression Regulation (mesh), Netherlands Twin Register (NTR), 3102 Bioinformatics and computational biology (for-2020), 3001 Agricultural biotechnology (for-2020), 11 Medical and Health Sciences (for), Medical and Health Sciences, 3105 Genetics (for-2020), Mice, Obesity (mesh), Animals (mesh), Genetic Predisposition to Disease (mesh), Cancer, Developmental Biology (science-metrix), Humans (mesh), Generic health relevance (hrcs-hc), Mice (mesh), Biological Sciences, Bioinformatics and computational biology, Phenotype (mesh), 06 Biological Sciences (for), Phenotype, Genome-Wide Association Study (mesh), Quantitative Trait Loci (mesh), 570, Genotype, Agricultural biotechnology, Quantitative Trait Loci, 610, SDG 3 - Good Health and Well-being, Genetics, Animals, Humans, Genetic Predisposition to Disease, Obesity, Obesity (rcdc), 31 Biological Sciences (for-2020), Genetics (rcdc), Genotype (mesh), Human Genome, Cancer (hrcs-hc), ta3121, Transcriptome (mesh), Human Genome (rcdc), Gene Expression Regulation, Generic health relevance, Transcriptome, Developmental Biology, Genome-Wide Association Study
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