A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity - PubMed (original) (raw)

. 2007 May 11;316(5826):889-94.

doi: 10.1126/science.1141634. Epub 2007 Apr 12.

Nicholas J Timpson, Michael N Weedon, Eleftheria Zeggini, Rachel M Freathy, Cecilia M Lindgren, John R B Perry, Katherine S Elliott, Hana Lango, Nigel W Rayner, Beverley Shields, Lorna W Harries, Jeffrey C Barrett, Sian Ellard, Christopher J Groves, Bridget Knight, Ann-Marie Patch, Andrew R Ness, Shah Ebrahim, Debbie A Lawlor, Susan M Ring, Yoav Ben-Shlomo, Marjo-Riitta Jarvelin, Ulla Sovio, Amanda J Bennett, David Melzer, Luigi Ferrucci, Ruth J F Loos, Inês Barroso, Nicholas J Wareham, Fredrik Karpe, Katharine R Owen, Lon R Cardon, Mark Walker, Graham A Hitman, Colin N A Palmer, Alex S F Doney, Andrew D Morris, George Davey Smith, Andrew T Hattersley, Mark I McCarthy

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A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity

Timothy M Frayling et al. Science. 2007.

Abstract

Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.

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Figures

Fig. 1

Fig. 1

Associations of SNPs in the FTO/KIA1005 region of chromosome 16 with (A) type 2 diabetes using 1924 cases and 2938 controls and (B) adult BMI in type 2 diabetic patients. (C) Linkage disequilibrium (_r_2) between associated SNP rs9939609 and all other SNPs in HapMap data in Caucasian European samples. (D) Gene positions.

Fig. 2

Fig. 2

(A and B) Meta-analysis plots for odds of (A) overweight and (B) obesity, compared with normal weight in adults for each copy of the A allele of rs9939609 carried. (C and D) Bar charts showing (C) DEXA-measured fat mass in 9-year-old children and (D) DEXA-measured lean mass in 9-year-old children, both from the ALSPAC study. Error bars represent 95% confidence intervals

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