Abstract
Gene–environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malmö Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 × 10−34), fat mass (P = 6.3 × 10−28) and fat-free mass (P = 1.3 × 10−24). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 × 10−4). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.Electronic supplementary materialThe online version of this article (doi:10.1007/s12263-013-0352-8) contains supplementary material, which is available to authorized users.
Highlights
Obesity is a globally increasing major health problem, and considerable evidence from twin, adoption and family studies demonstrates that around 40–70 % of population variation in body mass index (BMI) is accounted by genetic factors (Herrera and Lindgren 2010; Maes et al 1997; Stunkard et al 1990)
Of the tested 16 single-nucleotide polymorphisms (SNPs), 14 were directionally consistent with the results reported in the original genome-wide association studies (GWAS) concerning association with BMI, waist or hip circumference, and 11 SNPs reached statistical significance with at least one of these traits (Table 2)
Variants in/near fat mass and obesity-associated gene (FTO), MC4R, FAIM2, SEC16B and AIF1 associated with greater height and 11 SNPs associated with increased weight (Table 2)
Summary
Obesity is a globally increasing major health problem, and considerable evidence from twin, adoption and family studies demonstrates that around 40–70 % of population variation in body mass index (BMI) is accounted by genetic factors (Herrera and Lindgren 2010; Maes et al 1997; Stunkard et al 1990). Several studies of the fat mass and obesity-associated gene (FTO) have indicated that environmental factors such as diet composition and physical activity level may modify the genetic susceptibility to develop obesity (Andreasen et al 2008; Li et al 2012; Sonestedt et al 2011; Sonestedt et al 2009) Apart from those in FTO, several of the identified SNPs are located in or near genes clearly related to appetite regulation (Willer et al 2009), and recently, five of the novel obesity loci (SH2B1, KCTD15, MTCH2, NEGR1 and BDNF) were indicated to be associated with dietary macronutrient intake levels (Bauer et al 2009). The MONICA/KORA study comprising of 12,462 individuals found no evidence of nutritional intake or energy expenditure as mediators of genetic variant-BMI association (Holzapfel et al 2010)
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