Approved research

Exploring Diet/Lifestyle factors as causes and modifiers of genetic determinants of obesity and metabolic traits

Lay summary

We would like to investigate how environmental factors (e.g. (reported) dietary intake and essential lifestyle factors) correlate with obesity/metabolic trait. We will establish which factors are causes and which are consequences of obesity (i.e. preventive measures) through Mendelian randomisation. Moreover we'd explore which of these environmental factors modify the effect of the genetic risk score on obesity/metabolic traits. The research aims at better understanding of obesity genetics and identify modifiable lifestyle factors causally influencing obesity and other metabolic traits We will apply statistical methods to explore the causal effect of obesity/metabolic traits on environment and visa versa. These methods require genetic data and lifestyle information.This will inform us which modifiable environmental factor are more likely causes/consequences of obesity. Furthermore, we'll identify which of these factors modify association strength between body-mass-index associated SNPs and obesity. We need the entire cohort for this analysis as lifestyle and dietary factors are self reported, thus less reliable. In addition, since individual genetic variants have small impact on these lifestyle factors, we have to maximise the sample size to ensure robust estimates.

Scope extension:

We would like to investigate how environmental factors (e.g. (reported) dietary intake and essential lifestyle factors) correlate with obesity/metabolic trait. We will establish which factors are causes and which are consequences of obesity (i.e. preventive measures) through Mendelian randomisation. Moreover we'd explore which of these environmental factors modify the effect of the genetic risk score on obesity/metabolic traits.

As part of the investigation of the genetic underpinnings of obesity, we would like to extend our search from imputed SNPs to all sequence variants (exome and eventually full genome sequencing) and copy number variations (CNVs) identified from genotype (and eventually sequencing) data.

As we are exploring the consequences of obesity, (common and rare forms of) cardio-metabolic diseases are of central interest, for which we would like to dissect the contribution of environmental, genetic factors (including polygenic risk scores) and their interactions.