Genetics of dietary habits and obesity - a twin study.

Obesity has become a major health concern due to the increased risk of co-morbidities, resulting in decreased quality of life, stigmatization, reduced working ability and early death. This causes a great challenge for the health care systems and results in increased direct costs related to treatment of obesity and co-morbidities, as well as increased indirect costs related to reduced function and withdrawal from the labour market. Both between and within societies, large variation in the prevalence of overweight and obesity exists. This variation is caused by differences in environmental exposures as well as genetic differences between individuals, resulting in differentiated susceptibility to environmental exposures. The evidence for genetic influence on anthropometry has previously been established and has been estimated to be 60-70% based on twin studies. These inter-individual differences can, however, not explain the increase in obesity prevalence during the past 70 years. Environmental factors must therefore play an important role in the obesity epidemic. Habitual diet is one of many environmental factors that potentially contribute to the inter-individual differences in body fat mass, but only limited evidence for associations between habitual dietary intake and anthropometry exists. Differences in habitual dietary intake are also partly determined by differences in genes influencing smell and taste preferences. But, so far, only few studies have investigated genetic influences on dietary intake in adults and the interplay between diet, genes and obesity. The focus of the thesis was to investigate the genetic and environmental influence on habitual diet and obesity as well as the association between habitual diet and anthropometry. The thesis is based on structural equation modelling of twin data from the Danish Twin Registry with special focus on the GEMINAKAR twin study that was performed in 1997-2000. In this study, anthropometric traits of the twin pairs were measured and habitual dietary intake was assessed through a food frequency questionnaire (FFQ). When studying body fat mass in population-based studies, the phenotype used is often the body mass index (BMI). This measure does, however, not specify whether excess body mass is due to excess fat mass and how the body fat is distributed. Studying the genetic and environmental correlations between the anthropometry measures in the GEMINAKAR sample showed that the genetic correlations between BMI, fat mass index (FMI) and waist circumference were high in men and that the genetic correlations between BMI, FMI, waist and hip circumference were high in women. For all anthropometric phenotypes, significant residual genetic influence existed. Based on information about habitual diet from the FFQ the genetic influence on total energy intake, macronutrient intake, as well as intake of energy from 20 food groups, was estimated. The proportion of variation in dietary intake explained by variation in genes differed between the dietary traits under study but for the majority of dietary variables the genetic influence was 20-50%. Accordingly, both diet and anthropometry is influenced by genetic variation. In order to control for potential confounding by genetic variation and shared environment on the association between habitual diet and body fat, the monozygotic twin pairs were selected and the associations between intrapair differences in dietary intake and intrapair differences in anthropometry were studied. For the majority of dietary traits, no associations or only weak associations were found. The study showed, however, consistent positive associations between intake of sugar-sweetened soft drink and BMI, FMI and waist circumference in men. Gene-environment interaction models showed that while high physical activity is associated with a down-regulation of genes predisposing to obesity, such effects were not found for protein intake. In conclusion, the studies included in this thesis contribute to the relatively limited existing literature, with insight into genetic determinants of habitual dietary intake, pleiotropic influences on anthropometry, and the interplay between diet, genes and obesity.