Research article
Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
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* Corresponding author: Camilla H Andreasen cila@novonordisk.com
1 Steno Diabetes Center, 2820 Gentofte, Denmark
2 Novo Nordisk A/S, Medical and Science, Development Projects, 2880 Bagsværd, Denmark
3 Faculty of Health Science, University of Aarhus, 8000 Aarhus, Denmark
4 Department of General Practice, University of Aarhus, 8000 Aarhus, Denmark
5 Bristol-Meyers Squibb & Co., Discovery Medicine and Clinical Pharmacology, CV Metabolic Diseases, 08543-4000, Princeton, NJ, USA
6 Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
7 Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark
8 Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark
BMC Medical Genetics 2009, 10:17 doi:10.1186/1471-2350-10-17
Published: 26 February 2009Abstract
Background
A genome-wide scan in unrelated US Caucasians identified rs7001819 upstream of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) and multiple variants within catenin (cadherin-associated protein), β-like 1 (CTNNBL1) to associate strongly with body mass index (BMI). The most significantly associating variants within CTNNBL1 including rs6013029 and rs6020846 were additionally confirmed to associate with morbid obesity in a French Caucasian case-control sample. The aim of this study was to investigate the impact of these three variants on obesity, through analyses of obesity-related quantitative traits, and case-control studies in large study samples of Danes.
Methods
The FDFT1 rs7001819, CTNNBL1 rs6013029 and rs6020846 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising 18,014 participants ascertained from; the population-based Inter99 cohort (n = 6,514), the ADDITION Denmark screening study cohort (n = 8,662), and a population-based sample (n = 680) and a type 2 diabetic patients group (n = 2,158) from Steno Diabetes Center.
Results
Both CTNNBL1 variants associated with body weight and height with per allele effect sizes of 1.0 [0.3–0.8] kg and 0.6 [0.2–0.9] cm, respectively, for the rs6020846 G-allele. No association was observed with BMI and waist circumference. In case-control studies neither of the CTNNBL1 variants showed association with overweight, obesity or morbid obesity (rs6013029: Odds Ratio (OR)overweight = 1.02 [0.90–1.16], ORobesity = 1.09 [0.95–1.25], ORmorbidobesity = 1.26 [0.91–1.74]; rs6020846: ORoverweight = 1.05 [0.93–1.18], ORobesity= 1.13 [1.00–1.28], ORmorbidobesity = 1.17 [0.86–1.61]). However, in meta-analyses of the present and the previous study, both the rs6013029 T-allele and the rs6020846 G-allele increased the risk of developing morbid obesity (rs6013029: ORcombined = 1.36 [1.12–1.64], p = 0.002; rs6020846: ORcombined = 1.26 [1.06–1.51], p = 0.01), and obesity (rs6013029: ORcombined = 1.17 [1.04–1.31], p = 0.007; rs6020846: ORcombined = 1.17 [1.05–1.30], p = 0.004).
The FDFT1 rs7001819 C-allele showed no association with obesity-related quantitative measures or dichotomous measures of overweight, obesity and morbid obesity.
Conclusion
CTNNBL1 variants associated with body weight and height, and confer the risk of developing obesity in meta-analyses combining the present and a previous study. FDFT1 rs7001819 showed no association with obesity, neither when analysing quantitative traits nor when performing case-control studies of obesity.