Common Variation in the Fat Mass and Obesity-Associated (<i>FTO</i>) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population

Chang, Yi‐Cheng; Liu, Pi-Hua; Lee, Wei-Jei; Chang, Tien-Jyun; Yin, Jiuli; Li, Chung‐Yi; Kuo, Shan-Shan; Lee, Kuang-Chin; Chuang, Lee‐Ming

doi:10.2337/db08-0377

Cited by 210 publications

(197 citation statements)

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“…For rs9939609, each copy of the risk allele A was associated with a BMI increase of B0.50 kgm À2 in the overall and B0.81 kgm À2 in the girls, which is much higher than previously reported B0.37 kgm À2 in the Chinese adult population. 29 These findings suggest that these two genes may have more obvious effects on obesity-related indices during puberty.…”

Section: Discussionmentioning

confidence: 95%

Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty

et al. 2011

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OBJECTIVE: Genome-wide association studies (GWAS) have identified some common variants associated with obesity risk in European descents. However, their influences on obesity-related indices for the Chinese children at puberty are not widely clear yet. To address this question, we conducted a study that aims to examine effects of eight previously reported GWAS singlenucleotide polymorphisms (SNPs) on four obesity-related indices in a sample of Chinese children aged 10 --12 years. METHODS: Anthropometric indices were measured in 1688 children (10.8 ± 0.4 years, boys ¼ 877, girls ¼ 811) from Shanghai Children's Sleep Project. Eight SNPs within the NEGR1, TMEM18, GNPDA2, MTCH2, SH2B1, FTO, MC4R and KCTD15 genes were genotyped using matrix-assisted laser desorption/ionization --time of flight mass spectrometry. Linear regression and genetic additive model were used to test for the association betweens SNPs and obesity-related indices (weight, body mass index (BMI), waist-to-height ratio and body fat). RESULTS: Only two SNPs, rs6548238 (TMEM18) and rs9939609 (FTO), were associated with all obesity-related indices with Po0.05. After adjusting for multiple tests, rs9939609 is the only one significantly associated with the indices. SNPs, rs6548238 and rs9939609 explained 0.28% (P ¼ 0.03) and 0.54% (P ¼ 0.002) variance of BMI, respectively, that are almost two-fold of the previously GWAS-reported effects. In addition, rs6548238 was associated with four indices in boys, but not in girls. In contrast, rs9939609 showed a strong association only in girls. Six other SNPs, rs2815752 (NEGR1), rs10938397 (GNPDA2), rs10838738 (MTCH2), rs7498665 (SH2B1), rs17782313 (MC4R) and rs11084753 (KCTD15), were not associated with obesity (P40.05). CONCLUSIONS: Variants of TMEM18 and FTO are associated with obesity indices during puberty in Chinese children, but candidate SNPs of NEGR1, GNPDA2, MTCH2, SH2B1, MC4R and KCTD15 have no significant effects on obesity indices. The findings also suggest that obesity susceptibility genes may exert more obvious effects during children's puberty. In addition, gender differences may exist in various obesity-related genes.

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Section: Discussionmentioning

confidence: 95%

Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty

et al. 2011

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“…Second, previous studies have largely supported an additive effect of variants in FTO on obesity metrics (e.g., BMI) (1,11,(25)(26)(27). More recent reports, however, have argued in support of exploring nonadditive models of obesity-associated genes (e.g., dominant, recessive) (28).…”

Section: Discussionmentioning

confidence: 99%

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues

Rapuano

Zieselman

Kelley

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life.T he relationship between genes and sensitivity to environmental cues is elusive, yet it is paramount to understanding the development of potentially maladaptive human behaviors. The rising prevalence of obesity is a major public health concern that has been attributed to various factors, such as genetic susceptibility (1), and increases in the availability and marketing of calorie-dense foods (2). However, little is known about how genetic predisposition to obesity influences sensitivity to real-world food cues and contributes to the development of unhealthy eating behaviors.Previous neuroimaging studies have demonstrated that responses to food cues in reward-related regions of the brain, such as the nucleus accumbens (NAcc), predict weight gain in adulthood (3) and giving in to food temptations in daily life (4). Furthermore, structural differences in NAcc volume have been positively associated with body mass index (BMI) in adults (5, 6). Because the development of the NAcc precedes the development of prefrontal control systems (7), this structure is suggested to play a key role in motivating and establishing unhealthy eating behaviors early in the lifespan. Importantly, genetic factors are a known contributor to brain development (8) and may influence risky behaviors during childhood and adolescence by biasing the early development of anatomical structures underlying reward-related brain function.In addition, the notion that genes contribute to obesity has recently gained much attention. More specifically, the fat-mass and obesity-associated (FTO) rs9939609 polymorphism has been strongly related to increased BMI and adiposity across the lifespan, and is suggested to influence food intake and food choice, rather than energy expenditure (9-11). Those with two high-risk "A" alleles (AA) are at an enhanced risk for obesity compared with those with two low-risk "T" alleles (TT) or those who are heterozygous (AT) for the FTO rs9939609 polymorphism. Although the FTO gene is highly expressed in the brain (1), the mechanism by which this gene promotes unhealthy...

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“…2) the data from the genetic studies examining type 2 diabetes Those showing significant (black circles) and non-significant (white circles) association with BMI in Japanese are depicted. SNP rs numbers of individual loci are as follows: rs2815752 for NEGR1, rs10913469 for SEC16B, rs4854344 for TMEM18, rs7647305 for ETV5, rs10938397 for GNPDA2, rs2844479 for NCR3, rs6265 for BDNF, rs10838738 for MTCH2, rs7138803 for BCDIN3D, rs4788102 for SH2B1, rs6499640 for FTO(1), rs9939609 for FTO(2), rs12970134 for MC4R and rs29941 for KCTD15 association at the FTO locus [3,11,24,[32][33][34][35][36][37][38][39][40][41][42], our aim being to evaluate the relationship between BMI in the control group (or derived population) and the OR for type 2 diabetes. We detected no apparent relationship between the tested variables (p=0.15 for East Asians and p=0.41 for Europeans; Fig.…”

Section: Association Of Obesity Susceptibility Snps With Type 2 Diabetesmentioning

confidence: 99%

Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals

et al. 2011

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Aims/hypothesis In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes.Methods We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of the original, as well as from additional populations.Electronic supplementary material The online version of this article

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Common Variation in the Fat Mass and Obesity-Associated (FTO) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population

Cited by 210 publications

References 29 publications

Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty

Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues

Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals

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