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Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes

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 significantl...

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Autores principales: Andreasen, Camilla Helene, Mogensen, Mette Sloth, Borch-Johnsen, Knut, Sandbæk, Annelli, Lauritzen, Torsten, Almind, Katrine, Hansen, Lars, Jørgensen, Torben, Pedersen, Oluf, Hansen, Torben
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669074/
https://www.ncbi.nlm.nih.gov/pubmed/19245693
http://dx.doi.org/10.1186/1471-2350-10-17
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author Andreasen, Camilla Helene
Mogensen, Mette Sloth
Borch-Johnsen, Knut
Sandbæk, Annelli
Lauritzen, Torsten
Almind, Katrine
Hansen, Lars
Jørgensen, Torben
Pedersen, Oluf
Hansen, Torben
author_facet Andreasen, Camilla Helene
Mogensen, Mette Sloth
Borch-Johnsen, Knut
Sandbæk, Annelli
Lauritzen, Torsten
Almind, Katrine
Hansen, Lars
Jørgensen, Torben
Pedersen, Oluf
Hansen, Torben
author_sort Andreasen, Camilla Helene
collection PubMed
description 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], OR(obesity )= 1.09 [0.95–1.25], OR(morbidobesity )= 1.26 [0.91–1.74]; rs6020846: OR(overweight )= 1.05 [0.93–1.18], OR(obesity)= 1.13 [1.00–1.28], OR(morbidobesity )= 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: OR(combined )= 1.36 [1.12–1.64], p = 0.002; rs6020846: OR(combined )= 1.26 [1.06–1.51], p = 0.01), and obesity (rs6013029: OR(combined )= 1.17 [1.04–1.31], p = 0.007; rs6020846: OR(combined )= 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.
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spelling pubmed-26690742009-04-15 Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes Andreasen, Camilla Helene Mogensen, Mette Sloth Borch-Johnsen, Knut Sandbæk, Annelli Lauritzen, Torsten Almind, Katrine Hansen, Lars Jørgensen, Torben Pedersen, Oluf Hansen, Torben BMC Med Genet Research Article 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], OR(obesity )= 1.09 [0.95–1.25], OR(morbidobesity )= 1.26 [0.91–1.74]; rs6020846: OR(overweight )= 1.05 [0.93–1.18], OR(obesity)= 1.13 [1.00–1.28], OR(morbidobesity )= 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: OR(combined )= 1.36 [1.12–1.64], p = 0.002; rs6020846: OR(combined )= 1.26 [1.06–1.51], p = 0.01), and obesity (rs6013029: OR(combined )= 1.17 [1.04–1.31], p = 0.007; rs6020846: OR(combined )= 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. BioMed Central 2009-02-26 /pmc/articles/PMC2669074/ /pubmed/19245693 http://dx.doi.org/10.1186/1471-2350-10-17 Text en Copyright © 2009 Andreasen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Andreasen, Camilla Helene
Mogensen, Mette Sloth
Borch-Johnsen, Knut
Sandbæk, Annelli
Lauritzen, Torsten
Almind, Katrine
Hansen, Lars
Jørgensen, Torben
Pedersen, Oluf
Hansen, Torben
Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
title Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
title_full Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
title_fullStr Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
title_full_unstemmed Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
title_short Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes
title_sort studies of ctnnbl1 and fdft1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 danes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669074/
https://www.ncbi.nlm.nih.gov/pubmed/19245693
http://dx.doi.org/10.1186/1471-2350-10-17
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