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1.
Meta-analysis indicates that SNP rs9939609 within FTO is not associated with major depressive disorder (MDD) in Asian population.
Yao, Y, Wen, Y, Du, T, Sun, N, Deng, H, Ryan, J, Rao, S
Journal of affective disorders. 2016;:27-30
Abstract
BACKGROUND Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with heritability of up to 38%. The fat mass- and obesity-associated (FTO) gene, in particular the single nucleotide polymorphism (SNP) rs9939609, has been identified as a genetic risk loci associated with MDD. However, most prior studies have involved European and American populations. Whether rs9939609 is an true risk SNP for MDD in Asian populations remains inconclusive. METHODS In the present study, we conducted a meta-analysis of the association between rs9939609 and MDD in Asian populations by combining 5 available case-control samples totaling 6531 cases and 12,359 controls. RESULTS Our meta-analysis suggests that rs9939609 is not a risk SNP for MDD in Asian populations by fixed effect model (Z=1.04, P=0.30, OR=0.96, 95% CI=0.90-1.03). LIMITATIONS The age distribution and gender ratios were not matched well in the combined samples of cases and controls. Publication bias might be also considered with only a relatively small number of association studies of FTO rs9939609 with MDD in Asian populations. CONCLUSIONS The absence of association of rs9939609 with MDD in our Asian populations suggests a potential genetic heterogeneity in the susceptibility of MDD on this locus.
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Association between the FTOrs8050136 polymorphism and cancer risk: a meta-analysis.
Zhao, J, Huang, X, Yang, M, Li, M, Zheng, J
Familial cancer. 2016;(1):145-53
Abstract
A meta-analysis on cancer risk relevant to FTOrs8050136 polymorphism. To investigate the comprehensive effect of FTOrs8050136 polymorphism on cancer risk based on a pooled result. Carcinogenesis is closely related to obesity. Both obesity and cancer share common pathogenic factors such as hereditary susceptibility and environmental predisposition. Recently, several studies had reported that the FTOrs8050136 polymorphism, a genetic variation highly associated with obesity, can be a potential cancer risk factor, while these results were inconsistent. With the help of PubMed, EMBASE, Chinese National Knowledge Infrastructure considerable research was done for potential studies without language restriction. Pooled odds ratio combined with 95 % confidence interval was employed to evaluate the potential correlations, and subgroup analyses were performed based on the cancer types and ethnic populations. There were eight articles comprising 21,810 cases and 85,070 controls met the eligibility criteria. Overall, there was no significant association between the FTOrs8050136 polymorphism and cancer risk (P = 0.163). Subgroup analysis illustrated that no association existed between the FTOrs8050136 polymorphism and cancer risk in Caucasians (P = 0.809), Asians (P = 0.412) and the mixed population (P = 0.093). With regard to cancer types, the result suggested that the FTOrs8050136 polymorphism had no connection with pancreatic cancer (P = 0.089), endometrial cancer (P = 0.353), prostate cancer (P = 0.578), colorectal cancer (P = 0.054) and melanoma (P = 0.357), while the inverse result was obtained in the subgroup of papillary thyroid cancer (P = 0.010). The FTOrs8050136 polymorphism may be not associated with carcinogenesis apart from papillary thyroid cancer, and further studies are needed to investigate the potential correlation.
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Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population.
Phani, NM, Vohra, M, Rajesh, S, Adhikari, P, Nagri, SK, D'Souza, SC, Satyamoorthy, K, Rai, PS
Molecular genetics and genomics : MGG. 2016;(1):193-204
Abstract
Peroxisome proliferator-activated receptors (PPARγ), adiponectin (ADIPOQ) and fat mass and obesity-associated gene (FTO) have been reported as a key candidate genes for obesity, type 2 diabetes (T2D) susceptibility and insulin resistance, and we hypothesize that in the background of obesity, the effect of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) variant could potentially influence T2D susceptibility. To decipher a more accurate estimation toward its population-specific impact of these variants toward susceptibility to T2D, a case-control study, systematic review and a meta-analysis was performed in a South Asian population. A case-control analysis of 518 T2D cases and 518 controls of Karnataka origin were performed to analyze the association of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) on the risk of T2D. In addition, a systematic review and meta-analysis for PPARγ2 (rs1801282) and FTO (rs9939609) was elucidated from Asian population. Our investigation showed that PPARγ2 (rs1801282) and FTO (rs9939609) are associated with T2D susceptibility. When T2D cohort was further stratified according to the obesity status, PPARγ2 (rs1801282) and FTO (rs9939609) showed association with T2D only in the obese diabetic group and ADIPOQ (rs16861194) showed no difference in risk of susceptibility to the disease. The meta-analysis of PPARγ2 (rs1801282) showed population-specific association for T2D susceptibility as opposed to FTO (rs9939609) which showed no difference in population effect toward T2D susceptibility. In conclusion, our study showed that PPARγ2 (rs1801282) and FTO (rs9939609) variants are associated with T2D susceptibility when associated with adiposity in Indian population.
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Association of fat-mass and obesity-associated gene FTO rs9939609 polymorphism with the risk of obesity among children and adolescents: a meta-analysis.
Quan, LL, Wang, H, Tian, Y, Mu, X, Zhang, Y, Tao, K
European review for medical and pharmacological sciences. 2015;(4):614-23
Abstract
OBJECTIVE To elucidate the association of fat-mass and obesity-associated gene (FTO) rs9939609 polymorphism with obesity among children and adolescents. METHODS A literature search was conducted in PubMed, MEDLINE, Springer, and Google scholar to identify eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used for four models: co-dominant model (AA vs. TT, AT vs. TT), dominant model (AA + AT vs. TT), recessive model (AA vs. AT + TT), and allelic model (A vs. T). Subgroup analyses stratified by ethnicity (Caucasian, others) and participants (children, children and adolescents) were assessed under allelic model. The heterogeneity and publication bias were examined. RESULTS This meta-analysis included 12 eligible studies consisting 5,000 cases and 9,853 controls. The results revealed that FTO rs9939609 polymorphism was significantly associated with the increased risk of obesity in co-dominant model (AA vs. TT: OR = 1.91, 95% CI: 1.47-2.48, p < 0.01; AT vs. TT: OR = 1.18, 95% CI: 1.02-1.38, p = 0.03), dominant model (AA + AT vs. TT: OR = 1.47, 95% CI: 1.35-1.59, p < 0.01), recessive model (AA vs. AT + TT: OR = 1.79, 95% CI: 1.47-2.17, p < 0.01), and allelic model (A vs. T: OR = 1.39, 95% CI: 1.22-1.58, p < 0.01). Similar results were obtained for the subgroup analyses stratified by ethnicity and participants under allelic model. CONCLUSIONS FTO rs9939609 polymorphism is associated with the increased risk of obesity among children and adolescents, especially the homozygous carriers.
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Associations between FTO genotype and total energy and macronutrient intake in adults: a systematic review and meta-analysis.
Livingstone, KM, Celis-Morales, C, Lara, J, Ashor, AW, Lovegrove, JA, Martinez, JA, Saris, WH, Gibney, M, Manios, Y, Traczyk, I, et al
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2015;(8):666-78
Abstract
Risk variants of fat mass and obesity-associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrient intake has not been reviewed systematically. Our aim was to evaluate the potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in OVID MEDLINE, Scopus, EMBASE and Cochrane of associations between macronutrient intake and FTO genotype in adults. Beta coefficients and confidence intervals (CIs) were used for per allele comparisons. Random-effect models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213,173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal day(-1) (95% CI: 10.76, 2.16) lower total energy intake (P = 0.003). Total fat (P = 0.028) and protein (P = 0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P = 0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrient intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.
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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
Zimmermann, E, Ängquist, LH, Mirza, SS, Zhao, JH, Chasman, DI, Fischer, K, Qi, Q, Smith, AV, Thinggaard, M, Jarczok, MN, et al
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2015;(4):327-340
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Abstract
Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.
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FTO gene variant and risk of hypertension: a meta-analysis of 57,464 hypertensive cases and 41,256 controls.
He, D, Fu, M, Miao, S, Hotta, K, Chandak, GR, Xi, B
Metabolism: clinical and experimental. 2014;(5):633-9
Abstract
OBJECTIVES Recent studies have suggested that fat mass and obesity-associated gene (FTO) may predispose individuals to develop hypertension. However, the results have been inconsistent. We performed a meta-analysis to investigate the relationship of FTO gene variant with risk of hypertension and influence of body mass index (BMI) on this risk. MATERIALS/METHODS A systematic literature search in PubMed, Embase and ISI web of science databases was performed to identify eligible published literatures. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS A total of seven studies comprising 57,464 hypertensive cases and 41,256 controls met the inclusion criteria and were included in the meta-analysis. The FTO gene variant(s) showed significant association with the risk of hypertension (OR=1.16, 95% CI=1.07-1.25, P<0.001) which disappeared on adjustment for BMI (OR=1.04, 95% CI=0.98-1.10, P=0.162). In addition, stratified analysis demonstrated a significant association of the FTO variant with the risk of hypertension in obese subjects (OR=1.10, 95% CI=1.01-1.19, P=0.032) but not in non-obese individuals (OR=1.00, 95% CI=0.97-1.03, P=0.832). Subgroup analysis based on ethnicity showed significant association between FTO variant and hypertension in both European (OR=1.07, 95% CI=1.01-1.14, P=0.028) and Asian populations (OR=1.37, 95% CI=1.23-1.53, P<0.001). However, the association remained significant only in Asians (OR=1.17, 95% CI=1.01-1.35, P=0.035) but not in the Europeans (OR=1.02, 95% CI=0.97-1.07, P=0.390) on adjustment for BMI. CONCLUSIONS The present meta-analysis confirms that FTO genotype mediates obesity-related hypertension.
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FTO genetic variants and risk of obesity and type 2 diabetes: a meta-analysis of 28,394 Indians.
Vasan, SK, Karpe, F, Gu, HF, Brismar, K, Fall, CH, Ingelsson, E, Fall, T
Obesity (Silver Spring, Md.). 2014;(3):964-70
Abstract
OBJECTIVE To investigate the magnitude of association of FTO variants with obesity, type 2 diabetes (T2DM), and related traits among Asian Indians. METHODS Random-effect meta-analysis was performed on pooled data from eight studies (n = 28,394) for obesity and related traits and six studies (n = 24,987) for assessment of T2DM risk in Indians where FTO variants were reported. RESULTS The minor A-allele of the FTO variant rs9939609 was associated with increased risk of obesity (OR 1.15, 95% CI 1.08-1.21, p = 2.14 × 10(-) (5) ), BMI (β = 0.30 kg/m2, 95% CI 0.21-0.38, p = 4.78 × 10(-) (11) ) and other regional adiposity measurements [waist (β = 0.74 cm, 95% CI 0.49-0.99), HC (β = 0.52, 95% CI 0.26-0.78), and waist-hip ratio (WHR) (β = 0.002, 95% CI 0.001-0.004)] in Indians (p ≤ 0.001). An increased risk for T2DM (OR 1.11; 95% CI 1.04-1.19, p = 0.002) was observed, which attenuated when adjusted for age, gender, and BMI (OR 1.09; 95%CI 1.02-1.16, p = 0.01). CONCLUSIONS Our study provides evidence of association between common FTO variant and obesity risk among Indians with comparable effect sizes as in Caucasians. The attenuation of FTO-T2DM risk on BMI adjustment reinforces that BMI does not fully account for the adiposity effects among Asian Indians who are more centrally obese.
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Association between fat mass- and obesity-associated (FTO) gene polymorphism and polycystic ovary syndrome: a meta-analysis.
Cai, X, Liu, C, Mou, S
PloS one. 2014;(1):e86972
Abstract
AIMS: Many studies have investigated the relationship between FTO gene polymorphism and polycystic ovary syndrome (PCOS) susceptibility but revealed mixed results. In this study, we aimed to perform a meta-analysis to clarify this association. METHODS Published literature from PubMed, Embase and CNKI was retrieved. Meta-analysis was performed to calculate pooled odds ratio (OR) with 95% confidence interval (CI) using the random- or fix- effects model. RESULTS A total of 5 studies (4778 cases and 4272 controls) were included in our meta-analysis. The results suggested that FTO rs9939609 polymorphism (or its proxy) was marginally associated with PCOS risk after adjustment for body mass index (BMI) (OR = 1.26; 95%CI: 1.02-1.55). However, the marginal association was not stable after sensitivity analysis. In the subgroup analysis by ethnicity, the association was significant in East Asians (OR = 1.43, 95%CI = 1.30-1.59) but not in Caucasians (OR = 1.04, 95%CI = 0.85-1.29). CONCLUSIONS Our present meta-analysis indicated that FTO rs9939609 polymorphism (or its proxy) might not be associated with risk of PCOS in overall population. However, in East Asians, there might be a direct association between FTO variant and PCOS risk, which is independent of BMI (adiposity).
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The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression.
Samaan, Z, Anand, SS, Zhang, X, Desai, D, Rivera, M, Pare, G, Thabane, L, Xie, C, Gerstein, H, Engert, JC, et al
Molecular psychiatry. 2013;(12):1281-6
Abstract
Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.