ArticleBMC genomics2013
A Drosophila functional evaluation of candidates from human genome-wide association studies of type 2 diabetes and related metabolic traits identifies tissue-specific roles for dHHEX.
Article in BMC genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 44 citations in OpenAlex.
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- Streptozotocin induces brain glucose metabolic changes and alters glucose transporter expression in the Lobster cockroach; Nauphoeta cinerea (Blattodea: Blaberidae).Molecular and cellular biochemistry · 2021Article
- Functional Inactivation ofInternational journal of molecular sciences · 2021Article
- A multicomponent screen for feeding behaviour and nutritional status in Drosophila to interrogate mammalian appetite-related genes.Molecular metabolism · 2021Article
- An integrative tissue-network approach to identify and test human disease genes.Nature biotechnology · 2018Article
- A high throughput, functional screen of human Body Mass Index GWAS loci using tissue-specific RNAi Drosophila melanogaster crosses.PLoS genetics · 2018Article
- Non-mammalian models of multiple endocrine neoplasia type 2.Endocrine-related cancer · 2018Review
- Circulating glucose levels inversely correlate withCommunications biology · 2018Article
- Regulation of Carbohydrate Energy Metabolism inGenetics · 2017Review
- Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits.Disease models & mechanisms · 2017Review
- Drosophila as a Model for Diabetes and Diseases of Insulin Resistance.Current topics in developmental biology · 2017Review
- Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila.BMC genomics · 2016Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundGenome-wide association studies (GWAS) identify regions of the genome that are associated with particular traits, but do not typically identify specific causative genetic elements. For example, while a large number of single nucleotide polymorphisms associated with type 2 diabetes (T2D) and related traits have been identified by human GWAS, only a few genes have functional evidence to support or to rule out a role in cellular metabolism or dietary interactions. Here, we use a recently developed Drosophila model in which high-sucrose feeding induces phenotypes similar to T2D to assess orthologs of human GWAS-identified candidate genes for risk of T2D and related traits.
resultsDisrupting orthologs of certain T2D candidate genes (HHEX, THADA, PPARG, KCNJ11) led to sucrose-dependent toxicity. Tissue-specific knockdown of the HHEX ortholog dHHEX (CG7056) directed metabolic defects and enhanced lethality; for example, fat-body-specific loss of dHHEX led to increased hemolymph glucose and reduced insulin sensitivity.
conclusionCandidate genes identified in human genetic studies of metabolic traits can be prioritized and functionally characterized using a simple Drosophila approach. To our knowledge, this is the first large-scale effort to study the functional interaction between GWAS-identified candidate genes and an environmental risk factor such as diet in a model organism system.
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