| Autor: |
Pajukanta, P., Sinsheimer, J.S., Alvarez, M., Laakso, M., Garske, K.M., Comenho, C., Ko, A., Pisegna, J.R., Pan, D.Z., Robles, C.R., Ye, C.J., Benhammou, J.N., Mohlke, K.L., Miao, Z., Bhagat, Y.V. |
| Jazyk: |
angličtina |
| Předmět: |
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| Popis: |
Identifying gene���environment (G��E) interactions contributing to human cardiometabolic disorders is challenging. Here we apply a reverse G��E candidate search by deriving candidate variants from promoter���enhancer interactions that respond to dietary fatty acid challenge through altered chromatin accessibility in primary human adipocytes. We then test all variants residing in lipid-responsive open chromatin sites in adipocyte promoter���enhancer contacts for interaction effects between genotype and dietary saturated fat intake on body-mass index (BMI) in the UK Biobank. We discover 14 new G��E variants in 12 lipid-responsive promoters, including in well-known lipid-related genes (LIPE, CARM1 and PLIN2) and newly associated genes, such as LDB3, for which we provide further functional and integrative genomic evidence. We further identify 24 G��E variants in enhancers, for a total of 38 new G��E variants for BMI in the UK Biobank, demonstrating that molecular genomics data produced in physiologically relevant contexts can be applied to discover new functional G��E mechanisms in humans. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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