Body mass index (BMI) is generally recognized as an indication for underweight and obesity. As a multifactorial trait, BMI is infl uenced by both genetic and environment factors. Multiple genome-wide association studies have been performed to identify the genetic variants with limited success. Understanding the molecular basis that mediates environmental exposure and BMI can be more important for prevention of metabolic disorders. In this study, we focus on gene expression changes associated with BMI using monozygotic twins. Monozygotic twins that discordant for BMI are perfect subjects for transciptomics studies where the genetic variants, age and sex are controlled. Twins are selected from The Middle Aged Danish Twins Study with BMI measured and their gene expression profi les obtained using gene expression microarray. Gene expression was summarized to gene level and weighted gene-expression correlation network analysis (WGCNA) was used to cluster correlated genes into modules and test their association with BMI. We applied pair-wised analysis in testing both module-trait and gene-trait associations. There were 4 out of 24 modules found signifi cantly associated with BMI with p < 0.036, and gene ontology enrichment analysis of 919 genes in one modules suggested that these genes are highly related to several metabolic and cellular processes (cellular metabolic process, FDR 9.3e-7; organic substance metabolic process, FDR 1.0e-5; primary metabolic process, FDR 3.7e-5). Our results suggested diff erential gene expression regulation involved in multiple metabolic and biological processes that lead to diff erential BMI. Moreover, we show that the discordant twin design in combination with WGCNA, is an effi cient and powerful approach in transcriptomic studies.
|Status||Udgivet - okt. 2018|
|Begivenhed||American Society of Human Genetics 2018 - San Diego Convention Center in San Diego, California, San Diego, USA|
Varighed: 16. okt. 2018 → 20. okt. 2018
Konferencens nummer: 2018
|Konference||American Society of Human Genetics 2018|
|Lokation||San Diego Convention Center in San Diego, California|
|Periode||16/10/2018 → 20/10/2018|