Dataset Information

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals.

ABSTRACT: BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10^-4) and with the Han/Eskin random effects method (P = 1.4 × 10^-7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10^-8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTOConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

SUBMITTER: Rivera M

PROVIDER: S-EPMC5537566 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals.

Rivera Margarita M Locke Adam E AE Corre Tanguy T Czamara Darina D Wolf Christiane C Ching-Lopez Ana A Milaneschi Yuri Y Kloiber Stefan S Cohen-Woods Sarah S Rucker James J Aitchison Katherine J KJ Bergmann Sven S Boomsma Dorret I DI Craddock Nick N Gill Michael M Holsboer Florian F Hottenga Jouke-Jan JJ Korszun Ania A Kutalik Zoltan Z Lucae Susanne S Maier Wolfgang W Mors Ole O Müller-Myhsok Bertram B Owen Michael J MJ Penninx Brenda W J H BWJH Preisig Martin M Rice John J Rietschel Marcella M Tozzi Federica F Uher Rudolf R Vollenweider Peter P Waeber Gerard G Willemsen Gonneke G Craig Ian W IW Farmer Anne E AE Lewis Cathryn M CM Breen Gerome G McGuffin Peter P

The British journal of psychiatry : the journal of mental science 20170622 2

BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression an ...[more]

PMID: 28642257

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Project description:BackgroundFat-mass and obesity-associated (FTO) gene is a gene located in chromosome region 16q12.2. Genetic variants in FTO are associated with the obesity phenotype in European and Hispanic populations. However, this association still remains controversial in Asian population. We aimed to test the association of FTO genetic variants with obesity and obesity-related metabolic traits among children living in Beijing, China.MethodsWe genotyped FTO variants rs9939609 in 670 children (332 girls and 338 boys) aged 8-11 years living in Beijing, and analyzed its association with obesity and obesity-related metabolic traits. Overweight and obesity were defined by age- and sex-specific BMI reference for Chinese children. Obesity-related metabolic traits included fasting plasma glucose, lipid profiles, leptin, ghrelin, adiponectin and blood pressures.ResultsThe frequency of rs9939609 A allele was 12.2%, which was 21.9% for the heterozygote and 1.2% for the homozygote of the A allele. The obesity prevalence among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (36.4% vs. 22.6%, P=0.004). Compared to the carrier of TT genotype, the likelihood of obesity was 1.79 (95% confidence interval (95% CI) 1.20-2.67, P=0.004) for the carrier of AA/AT genotype, after adjustment of sex, age and puberty stages. The BMI Z-score of children with AA/AT genotype were significantly higher than that of their counterparts with the TT genotype (1.1±0.1 vs. 0.8±0.1, P=0.02). The concentration of triglyceride was 1.03±0.52 mmol/L among TT carrier and 1.13±0.68 mmol/L among AA/AT carrier (P=0.045). While, the concentrations of adiponectin were 18.0±0.4 μg/ml among carriers of TT and 16.2±0.7 μg/ml among subjects with AA/AT genotype (P=0.03). The level of glucose marginally increased in the AA/AT genotype subjects (4.67±0.40 mmol/L vs. 4.60±0.35 mmol/L, P=0.08). The evidence of association was reduced after adjustment for BMI (P=0.38 for triglyceride, P=0.20 for adiponectin and glucose). There was weak evidence of association between rs9939609 and other obesity-related metabolic traits including total cholesterol (3.92±0.03 mmol/L vs. 4.02±0.05 mmol/L, P=0.10), insulin (2.69±1.77 ng/ml vs. 3.12±2.91 ng/ml, P=0.14), and insulin resistance (HOMA-IR 0.56±0.03 vs. 0.66±0.05, P=0.10).ConclusionsGenetic variation in the FTO gene associates with obesity in Chinese children.

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Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals.

Publications

Interaction between the <i>FTO</i> gene, body mass index and depression: meta-analysis of 13701 individuals.

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