(29-09-09) Obesity genes identified in genome-wide association studies are associated with adiposity measures

and potentially with nutrient-specific food preference1,2,3




Florianne Bauer, Clara C Elbers, Roger AH Adan, Ruth JF Loos, N Charlotte Onland-Moret, Diederick E Grobbee, Jana V van Vliet-Ostaptchouk, Cisca Wijmenga and Yvonne T van der Schouw

1 From the Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands (FB, CCE, NCO-M, and CW); the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands (FB, CCE, NCO-M, DEG, and YTvdS); the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands (CW); the Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, Netherlands (RAHA); the Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands (JVvV-O); and the MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom (RJFL).
2 Supported by SenterNovem (IOP Genomics IGE05012).
3 Address correspondence to YT van der Schouw, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands. E-mail: [email protected] .
Background: New genetic loci, most of which are expressed in the brain, have recently been reported to contribute to the development of obesity. The brain, especially the hypothalamus, is strongly involved in regulating weight and food intake.
Objectives: We investigated whether the recently reported obesity loci are associated with measures of abdominal adiposity and whether these variants affect dietary energy or macronutrient intake.
Design: We studied 1700 female Dutch participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Their anthropometric measurements and intake of macronutrients were available. Genotyping was performed by using KASPar chemistry. A linear regression model, with an assumption of an additive effect, was used to analyze the association between genotypes of 12 single nucleotide polymorphisms (SNPs) and adiposity measures and dietary intake.
Results: Seven SNPs were associated (P < 0.05) with weight, body mass index (BMI), and waist circumference (unadjusted for BMI). They were in or near to 6 loci: FTO, MC4R, KCTD15, MTCH2, NEGR1, and BDNF. Five SNPs were associated with dietary intake (P < 0.05) and were in or near 5 loci: SH2B1 (particularly with increased fat), KCTD15 (particularly with carbohydrate intake), MTCH2, NEGR1, and BDNF.
Conclusions: We confirmed some of the findings for the newly identified obesity loci that are associated with general adiposity in a healthy Dutch female population. Our results suggest that these loci are not specifically associated with abdominal adiposity but more generally with obesity. We also found that some of the SNPs were associated with macronutrient-specific food intake.

Source: American Journal of Clinical Nutrition, doi:10.3945/ajcn.2009.27781
Vol. 90, No. 4, 951-959, October 2009

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