Dataset Information

Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.

ABSTRACT: The underlying genetic component of obesity-related traits is not well understood, and there is limited evidence to support genetic association shared across multiple studies, populations, and environmental contexts. The present study investigated the association between candidate variants and obesity-related traits in a sample of 1,886 adult Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort.We selected and genotyped 19 single nucleotide polymorphisms in 10 genes (ADRB2, ADRB3, FTO, GNB3, INSIG2, LEPR, PPARG, TNF, UCP2, and UCP3) that had been previously reported to be associated with an obesity-related quantitative trait.We observed evidence for association of the A allele of rs9939609 (FTO intron 1) with increased BMI (P = 0.0072 before multiple test correction), baseline BMI (P = 0.0015), longitudinal BMI based on eight surveys from 1983 to 2005 (P = 0.000029), waist circumference (P = 0.0094), and weight (P = 0.021). The increase in average BMI was approximately 0.4 for each additional A allele. We also observed association of the ADRB3 Trp64Arg variant with BMI, waist circumference, percent body fat, weight, fat mass, arm fat area, and arm muscle area (P < 0.05), although the direction of effect is inconsistent with the majority of previous reports.Our study confirms that FTO is a common obesity susceptibility gene in Filipinos, with an effect size similar to that seen in samples of European origin.

SUBMITTER: Marvelle AF

PROVIDER: S-EPMC2453620 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.

Marvelle Amanda F AF Lange Leslie A LA Qin Li L Adair Linda S LS Mohlke Karen L KL

Diabetes 20080421 7

<h4>Objective</h4>The underlying genetic component of obesity-related traits is not well understood, and there is limited evidence to support genetic association shared across multiple studies, populations, and environmental contexts. The present study investigated the association between candidate variants and obesity-related traits in a sample of 1,886 adult Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort.<h4>Research design and methods</h4>We selected and ...[more]

PMID: 18426866

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Project description:The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7)), hip circumference (p = 3.4 x 10(-8)), and weight (p = 9.1 x 10(-7)). In Sardinia, homozygotes for the rare "G" allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common "A" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6)). Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.

Project description:Background and aimsObesity is a growing public health concern in Bangladesh, which is influenced by a complex interplay of genetic and environmental factors. The genetic variant rs9939609 of the FTO (fat mass and obesity-associated) gene has been found to be associated with an increased risk for obesity, depending on the population studied. The purpose of this cross-sectional study is to examine the relationship between the FTO gene polymorphism (rs9939609) and lifestyle-related risk factors, and their impact on obesity-related traits and biochemical parameters in the Bangladeshi population.MethodsA total of 280 participants were enrolled in this study, comprising of 140 individuals with overweight and obesity (body mass index [BMI] ≥ 23.0) and 140 non-overweight healthy individuals (18.5 ≤ BMI ≥ 22.9). Demographic information, dietary behaviors, and physical activity-related data were collected using a structured questionnaire. Additionally, anthropometric assessments and measurements of biochemical parameters such as lipid profile and C-reactive protein were performed. The amplification refractory mutation system-polymerase chain reaction technique was used to identify single-nucleotide polymorphism in the FTO gene. Descriptive statistics, χ,2 and one-way ANOVA were performed to evaluate the relationships between independent and dependent variables.ResultsThe presence of rs9939609 was strongly associated with the obesity risk factors of increased BMI, cholesterol, triglycerides, and low-density lipoprotein. We also found a significant association (p < 0.05) of rs9939609 with overweight and obesity in codominant AA versus TT (odds ratio [OR] = 0.299, 95% CI: 0.129-0.695) and AA versus AT (OR = 2.273, 95% CI: 1.023-5.053), recessive TT versus AA+AT (OR = 5.154, 95% CI: 2.463-10.782), and overdominant AT versus AA+TT (OR = 0.244, 95% CI: 0.122-0.488) models.ConclusionFTO variant rs9939609 is significantly linked to obesity and an increased risk of hyperlipidemia in the Bangladeshi population. However, this association is intertwined with environmental factors such as diet and physical activity.

Dataset Information

Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.

Publications

Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.

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