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- Title
FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life.
- Authors
Hertel, Jens K.; Johansson, Stefan; Sonestedt, Emily; Jonsson, Anna; Lie, Rolv T.; Platou, Carl G. P.; Nilsson, Peter M.; Rukh, Gull; Midthjell, Kristian; Hveem, Kristian; Melander, Olle; Groop, Left; Lyssenko, Valeriya; Molven, Anders; Orho-Melander, Marju; Njølstad, Pål R.
- Abstract
OBJECTIVE--FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span. RESEARCH DESIGN AND METHODS--Through regression models, we ,assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians. RESULTS--The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 x 10-8) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 x 10-8). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m² per risk allele; P = 2.0 x 10-26), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (ΔBMI = 0.0 [-0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS--We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter.
- Subjects
TYPE 2 diabetes; WEIGHT gain; GENETIC polymorphisms; OBESITY; BODY mass index
- Publication
Diabetes, 2011, Vol 60, Issue 5, p1637
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db10-1340