Genetic variation of FTO: rs1421085 T&gt;C, rs8057044 G&gt;A, rs9939609 T&gt;A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

González-Herrera, Lı́zbeth; Zavala-Castro, Jorge; Ayala-Cáceres, Claudia; Pérez-Mendoza, Gerardo; López-González, María José; Pinto-Escalante, Doris; Canto-Cetina, Thelma; García-Escalante, María Guadalupe; Rubí-Castellanos, Rodrigo; Contreras-Capetillo, Silvina; Fernando, Herrera‐Sanchez; Méndez-Domínguez, Nina; Alcocer-Gamboa, Alberto

doi:10.1002/ajhb.23192

Cited by 27 publications

(19 citation statements)

References 42 publications

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“…As expected, the majority of the resulting associations were found in SNPs that lie within the FTO gene. This gene has been associated to BMI and obesity in several studies and is a major focal point in obesity-related research (Scuteri et al 2007;Frayling et al 2007;Dina et al 2007;Zeggini et al 2007;Hinney et al 2007;Hunt et al 2008;Price et al 2008;Grant et al 2008;Hotta et al 2008;Loos et al 2008;Tan et al 2008;Villalobos-Comparán et al 2008;Thorleifsson et al 2008;Willer et al 2009;Meyre et al 2009;Wing et al 2009;Shimaoka et al 2010;Fawcett and Barroso 2010;Wang et al 2011;Prakash et al 2011;Okada et al 2012;Berndt et al 2013;Wheeler et al 2013;Graff et al 2013;Olza et al 2013;Qureshi et al 2017;González-Herrera et al 2019). Moreover, the two strongest associations in the GWAS were from SNPs in FTO (rs1558902/ rs1421085, p = 1.67x10 -7 /1.75x10 -7 ), highlighting the overall importance of this gene in relation to obesity.…”

Section: Gwas Of Healthy Nevada Bmi and Obesitymentioning

confidence: 99%

“…This study presents first a GWAS of BMI in a cohort without DM2, followed by a GWAS of a cohort with DM2, to identify the differences in the genetic mechanisms of obesity (BMI $30) without DM2 and with DM2, and show that DM2 is indeed, an important predictor of high BMI when included as comorbidity. Although a number of large meta-analyses of multiple genome-wide association studies (GWASs) have detected possible causative single nucleotide polymorphisms (SNPs) of obesity and increased BMI (Scuteri et al 2007;Frayling et al 2007;Dina et al 2007;Zeggini et al 2007;Yanagiya et al 2007;Hinney et al 2007;Hunt et al 2008;Price et al 2008;Grant et al 2008;Hotta et al 2008;Loos et al 2008;Tan et al 2008;Villalobos-Comparán et al 2008;Thorleifsson et al 2008;Willer et al 2009;Meyre et al 2009;Wing et al 2009;Liu et al 2010;Shimaoka et al 2010;Fawcett and Barroso 2010;Speliotes et al 2010;Wang et al 2011;Prakash et al 2011;Okada et al 2012;Cha et al 2012;Berndt et al 2013;Wheeler et al 2013;Graff et al 2013;Olza et al 2013;Boender et al 2014;Qureshi et al 2017;Hudek et al 2018;González-Herrera et al 2019), none, to the best of our knowledge, have included comprehensive GWASs on the quantitative BMI metric and on extreme obesity case-control simultaneously, as well as investigated phenotypic associations with BMI, obesity, and significant loci identified by the GWAS.…”

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confidence: 99%

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A Comprehensive Genome-Wide and Phenome-Wide Examination of BMI and Obesity in a Northern Nevadan Cohort

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Lombardi

et al. 2020

G3 Genes|Genomes|Genetics

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The aggregation of Electronic Health Records (EHR) and personalized genetics leads to powerful discoveries relevant to population health. Here we perform genome-wide association studies (GWAS) and accompanying phenome-wide association studies (PheWAS) to validate phenotype-genotype associations of BMI, and to a greater extent, severe Class 2 obesity, using comprehensive diagnostic and clinical data from the EHR database of our cohort. Three GWASs of 500,000 variants on the Illumina platform of 6,645 Healthy Nevada participants identified several published and novel variants that affect BMI and obesity. Each GWAS was followed with two independent PheWASs to examine associations between extensive phenotypes (incidence of diagnoses, condition, or disease), significant SNPs, BMI, and incidence of extreme obesity. The first GWAS examines associations with BMI in a cohort with no type 2 diabetics, focusing exclusively on BMI. The second GWAS examines associations with BMI in a cohort that includes type 2 diabetics. In the second GWAS, type 2 diabetes is a comorbidity, and thus becomes a covariate in the statistical model. The intersection of significant variants of these two studies is surprising. The third GWAS is a case vs. control study, with cases defined as extremely obese (Class 2 or 3 obesity), and controls defined as participants with BMI between 18.5 and 25. This last GWAS identifies strong associations with extreme obesity, including established variants in the FTO and NEGR1 genes, as well as loci not yet linked to obesity. The PheWASs validate published associations between BMI and extreme obesity and incidence of specific diagnoses and conditions, yet also highlight novel links. This study emphasizes the importance of our extensive longitudinal EHR database to validate known associations and identify putative novel links with BMI and obesity.

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Section: Gwas Of Healthy Nevada Bmi and Obesitymentioning

confidence: 99%

mentioning

confidence: 99%

A Comprehensive Genome-Wide and Phenome-Wide Examination of BMI and Obesity in a Northern Nevadan Cohort

Schlauch

Read

Lombardi

et al. 2020

G3 Genes|Genomes|Genetics

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“…Although the impact of environmental factors, like a sedentary lifestyle and excessive nutrient supply, has a large contribution to the end result, more attention should be paid to other relevant obesity-related factors [ 4 ]. Many studies, also in the pediatric population, focus on single nucleotide polymorphisms (SNPs) in genes with a well-described relationship with obesity, such as FTO [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], or genes, whose role in obesity is recently gradually being discovered, as the PLAG1 gene [ 16 , 17 , 18 ]. However, very few studies address the impact of epigenetics, including the DNA methylation of CpG dinucleotides, on this phenomenon [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose–Lipid Metabolism

Czogała

Strojny

et al. 2021

Nutrients

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The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.

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“…Also, in Mexican children (aged 6.1 to 12.3 years), the FTO rs9939609 variant was associated with obesity‐related traits including BMI ( P = .03), WC ( P = .02), triceps skinfold ( P = .03), and WHtR ( P = .01) and with increased risk for alterations in lipid profiles (Muñoz‐Yáñez et al, ). More recently, a study based on a sample of 318 school‐aged children (6‐12 years old) with Mayan ethnicity observed a differential association for boys and girls for the FTO SNPs rs1421085, rs8057044, and rs9939609 and the genetic risk for obesity or overweight status: FTO rs1421085 and rs9939609 were associated with genetic susceptibility for obesity in girls, whereas rs8057044 was associated with overweight only in boys (González‐Herrera et al, ). Furthermore, the role of several FTO variants, including rs9939609, in gender‐specific development of childhood obesity has been previously suggested (Jacobson et al, ).…”

Section: Discussionmentioning

confidence: 99%

Physical activity and the association between the FTO rs9939609 polymorphism and obesity in Portuguese children aged 3 to 11 years

Manco

Pinho

Albuquerque

et al. 2019

American J Hum Biol

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Objectives: To investigate whether objectively measured physical activity (PA) modulates the association between the FTO rs9939609 polymorphism and obesity variables in a sample of Portuguese children. Methods: A total of 440 children (213 girls and 227 boys) aged 3 to 11 years were observed. Genotyping was performed using TaqMan assay. Body mass index (BMI), BMI Z scores, waist circumference (WC), and waist-to-height ratio (WHtR) were calculated. PA was estimated in 399 children by accelerometry. Results: Linear regression, in the additive model, showed that the rs9939609 minor A-allele significantly associated with BMI (P = .029), BMI Z score (P = .017), WC (P = .016), and WHtR (P = .019). Logistic regression, in the additive model, showed a marginally significant association between the A-allele and overweight/obesity (odds ratio [OR]: 1.372; P = .049). When stratified by sex, rs9939609 showed marginal or significant associations with BMI (P = .08), BMI Z score (P = .07), WC (P = .005), WHtR (P = .02), and overweight/obesity (OR: 1.529; P = .064) in girls but not in boys (P > .05). Significant interactions were not found between the FTO polymorphism and PA (inactive vs active groups of children) for BMI (P = .461), BMI Z score (P = .387), WC (P = .757), or WHtR (P = .621). Conclusions: Findings of the present study highlight the association between FTO rs9939609 and obesity or body fat indices in girls but not in boys. PA was not found to mediate the impact of FTO genetic variation on risk of obesity.

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Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

Cited by 27 publications

References 42 publications

A Comprehensive Genome-Wide and Phenome-Wide Examination of BMI and Obesity in a Northern Nevadan Cohort

A Comprehensive Genome-Wide and Phenome-Wide Examination of BMI and Obesity in a Northern Nevadan Cohort

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose–Lipid Metabolism

Physical activity and the association between the FTO rs9939609 polymorphism and obesity in Portuguese children aged 3 to 11 years

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