British Journal of Nutrition

Full Papers

Human and Clinical Nutrition

Genetic predisposition to obesity and lifestyle factors – the combined analyses of twenty-six known BMI- and fourteen known waist:hip ratio (WHR)-associated variants in the Finnish Diabetes Prevention Study

Tiina Jääskeläinena1 c1, Jussi Paananena1, Jaana Lindströma2, Johan G. Erikssona2a3a4a5a6, Jaakko Tuomilehtoa2a7a8, Matti Uusitupaa1a9 and for the Finnish Diabetes Prevention Study Groupa1

a1 Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, PO Box 1627, FI-70211 Kuopio, Finland

a2 Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

a3 Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland

a4 Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland

a5 Folkhälsan Research Centre, Helsinki, Finland

a6 Vasa Central Hospital, Vasa, Finland

a7 Center for Vascular Prevention, Danube-University Krems, Krems, Austria

a8 South Ostrobothnia Central Hospital, Seinäjoki, Finland

a9 Research Unit, Kuopio University Hospital, Kuopio, Finland


Recent genome-wide association studies have identified multiple loci associated with BMI or the waist:hip ratio (WHR). However, evidence on gene–lifestyle interactions is still scarce, and investigation of the effects of well-documented dietary and other lifestyle data is warranted to assess whether genetic risk can be modified by lifestyle. We assessed whether previously established BMI and WHR genetic variants associate with obesity and weight change in the Finnish Diabetes Prevention Study, and whether the associations are modified by dietary factors or physical activity. Individuals (n 459) completed a 3 d food record and were genotyped for twenty-six BMI- and fourteen WHR-related variants. The effects of the variants individually and in combination were investigated in relation to obesity and to 1- and 3-year weight change by calculating genetic risk scores (GRS). The GRS were separately calculated for BMI and the WHR by summing the increasing alleles weighted by their published effect sizes. At baseline, the GRS were not associated with total intakes of energy, macronutrients or fibre. The mean 1- and 3-year weight changes were not affected by the BMI or WHR GRS. During the 3-year follow-up, a trend for higher BMI by the GRS was detected especially in those who reported a diet low in fibre (P for interaction = 0·065). Based on the present findings, it appears unlikely that obesity-predisposing variants substantially modify the effect of lifestyle modification on the success of weight reduction in the long term. In addition, these findings suggest that the association between the BMI-related genetic variants and obesity could be modulated by the diet.

(Received September 28 2012)

(Revised January 22 2013)

(Accepted March 08 2013)

(Online publication May 14 2013)

Key Words:

  • Obesity;
  • Genetics;
  • Polymorphisms;
  • Lifestyles;
  • Diets;
  • Interactions;
  • Interventions


c1 Corresponding author: T. Jääskeläinen, fax +358 17 163 2792, email


  Abbreviations: DPS, Diabetes Prevention Study; FTO, fat mass- and obesity-associated gene; GRS, genetic risk scores; WHR, waist:hip ratio