Title of project

Variant-to-function translation of obesity-associated loci through multi-omics data integration

Abstract

Background: Obesity has reached epidemic levels in many countries. It is not only an important risk factor for conditions such as type 2 diabetes and cardiovascular disease, but a serious complex disease in its own that needs to be specifically addressed. Even though environmental factors play a critical role in the development of obesity, genetic studies have shown that genetic variation accounts for up to 70% of variation in obesity susceptibility. Genome-wide association studies (GWASs) for body mass index (BMI) have so far identified hundreds of genetic risk loci, but only a handful have been successfully translated into biological insights. In recent years, biobank-scale multi-omics assays have been conducted on thousands of individuals, revolutionizing the molecular epidemiology field, and providing an unprecedented opportunity for high-throughput variant-to-function translation.

Aim: The main aim of my project is to translate GWAS-identified BMI-associated loci into new biology underlying body weight regulation and obesity susceptibility. To that extent, I will identify the molecular biomarkers, the target cell types, and the cell-type-specific molecular effects that mediate the association between each locus with BMI.

Approach: I will implement cutting-edge computational and statistical genetic approaches to expedite this variant-to-function translation. I will integrate the largest, most comprehensive population-scale multi-omics data (genomics, transcriptomics, proteomics, metabolomics) of studies such as the deCODE Health study, the UK Biobank and the Holbæk Study, with the latest BMI GWAS summary statistics of the GIANT Consortium. Besides whole-body omics data, I will leverage cell-type-specific imaging and omics data, generated from unique samples by Dr. Melina Claussnitzer’s team at the Novo Nordisk Foundation Center for Genomic Mechanisms of Disease at the Broad Institute, during 3-month research stay.

Implications: Guided by exciting preliminary findings, I expect to identify new biomarkers that lead to new insights into the biology that underlies body weight regulation. The findings of this project may pave the way towards new targets for the treatment and prevention of obesity. Furthermore, I expect that the integrative approach implemented in my project, applied more broadly, can also accelerate the variant-to-function translation for other complex traits, including cardiometabolic diseases.