Reverse gene–environment interaction approach to identify variants influencing body-mass index in humans

Abstract

Identifying gene-environment interactions (GxEs) contributing to human cardiometabolic disorders is challenging. Here we apply a reverse GxE candidate search by deriving candidate variants from promoter-enhancer interactions that respond to dietary fatty acid challenge through altered chromatin accessibility in human primary adipocytes. We then test all variants residing in the lipid-responsive open chromatin sites within adipocyte promoter-enhancer contacts for interaction effects between the genotype and dietary saturated fat intake on body mass index (BMI) in the UK Biobank. We discover 14 novel GxE variants in 12 lipid-responsive promoters, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

TMT-based quantitative proteomics analysis reveals the key proteins related with the differentiation process of goat intramuscular adipocytes

“…LDB3 was well known for its role in myofibrillar myopathies. Recent study found that the LDB3 promoter responds to lipid uptake in human adipose tissue [ 57 ]. AIF1L protein seemed to exist in all adipose tissue.…”

Integrative analysis of liver-specific non-coding regulatory SNPs associated with the risk of coronary artery disease

“…The promoter Capture Hi-C assay was performed using two replicates of 10 million HepG2 cells, as described previously. 25 The libraries were sequenced on the Illumina HiSeq 4000 platform. On average, 114.4 M paired-end reads were obtained per sample.…”

Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma

“…Beyond germ-like mutations that may predispose to disease, which has largely been the focus of genetic studies in NAFLD, heritable epigenetic changes also have an important role in NAFLD-associated HCC which include but are not limited to DNA methylation, chromosomal looping interactions, RNA modifications and the emerging role of non-coding RNAs [ 54 – 57 ] . Additionally, several studies have applied circulating tumor DNA (cfDNA) methods to further study HCC [ 58 , 59 ] , which has not only shed some light on the biology of HCC but is also promising for use as a biomarker in the future.…”

“…Additionally, several studies have applied circulating tumor DNA (cfDNA) methods to further study HCC [ 58 , 59 ] , which has not only shed some light on the biology of HCC but is also promising for use as a biomarker in the future. The identification of these epigenetic modifications points to further understanding of gene regulation changes, which are influenced by their environment [ 54 ] .…”

“…The TM6SF2 gene is involved in regulating liver fat metabolism, lipoprotein secretion and hepatic lipid droplet content Kozlitina et al [46] Falleti et al [47] Vespasiani-Gentilucci et al [140] rs641738 C>T The MBOAT7 gene encodes a protein known as Lysophospholipid acyltransferase 7 that is involved in the re-acylation of phospholipids as part of the phospholipid remodeling pathway Mancina et al [48] Luukkonen et al [49] Donati et al [50] Beyond germ-like mutations that may predispose to disease, which has largely been the focus of genetic studies in NAFLD, heritable epigenetic changes also have an important role in NAFLD-associated HCC which include but are not limited to DNA methylation, chromosomal looping interactions, RNA modifications and the emerging role of non-coding RNAs [54][55][56][57] . Additionally, several studies have applied circulating tumor DNA (cfDNA) methods to further study HCC [58,59] , which has not only shed some light on the biology of HCC but is also promising for use as a biomarker in the future.…”