Is the adiposity‐associated <scp><i>FTO</i></scp> gene variant related to all‐cause mortality independent of adiposity? Meta‐analysis of data from 169,551 <scp>C</scp>aucasian adults

Zimmermann, Esther; Ängquist, Lars; Mirza, Saad; Zhao, Jingjing; Chasman, Daniel I.; Fischer, Kai; Qi, Qi; Smith, Ashley; Thinggaard, Mikael; Jarczok, Marc N.; Nalls, Michael A.; Trompet, Stella; Timpson, Nicholas J.; Schmidt, Börge; Jackson, Anvesh; Lyytikäinen, Leo-Pekka; Verweij, Niek; Mueller-Nurasyid, Martina; Vikström, Max; Marques‐Vidal, Pedro; Wong, Andrew; Meidtner, Karina; Middelberg, Rita P. S.; Strawbridge, Rona J.; Christiansen, L; Kyvik, Kirsten Ohm; Hamsten, Anders; Jääskeläinen, Tiina; Tjønneland, Anne; Eriksson, Johan G.; Whitfield, John B.; Boeing, Heiner; Hardy, Rebecca; Vollenweider, P.; Leander, Karin; Peters, Annette; Harst, Pim van der; Lehtimäki, Terho; Meirhaeghe, Aline; Tuomilehto, Jaakko; Joeckel, Karl-Heinz; Ben-Shlomo, Yoav; Sattar, Naveed; Baumeister, Sebastian E.; Smith, George Davey; Casas, Juan-Pablo; Houston, Denise K.; Maerz, Winfried; Christensen, Kaare; Gudnason, Vilmundur; Hu, Frank B.; Metspalu, Andres; Ridker, Paul M.; Wareham, Nicholas J.; Loos, Ruth J.F.; Tiemeier, Henning; Sonestedt, Emily; Sørensen, Thorkild I. A.

doi:10.1111/obr.12263

Cited by 9 publications

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“…This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality, but Zimmermann et al (2014) did not found that FTO SNP is associated with allcause mortality independently of the adiposity phenotypes in comparing with previous investigated studies. Zimmermann et al (2014) found that the minor allele of the FTO SNP was associated with higher BMI (n = 169,551; 0.32 kg m ). Subsequently, Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor…”

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confidence: 36%

Effect of FTO rs1121980 to Body Mass Index

Candráková

Trakovická

Candrák

et al. 2016

Acta fytotechn zootechn

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The aim of this study was to investigate the effect of selected polymorphism FTO rs1121980 on body mass index in humans. In the study participated 79 people from Slovakia with some genetic relatedness. The column kit has been used to isolate the genomic DNA from a buccal swab. Genotyping of single nucleotide polymorphism rs1121980 of FTO gene was performed by amplification-refractory mutation system (ARMS). The most common genotype was found in heterozygous form (CT = 0.4051). The least frequent genotype in FTO was CC (0.2911) and the minor C allele reached frequency 0.49365. The FTO gene had increased frequency of T allele (0.50635). According to the results it can be assumed that the genotype CC (FTO rs1121980) has a protective effect on the prevalence of obesity compared to the other genotypes. With adding of the anthropometric measurements, blood test and extension of the group, the statistical relevance could increase in the future in relation to obesity.Keywords: body mass index (BMI), FTO gene, human obesity, SNP polymorphism, rs1121980 IntroductionThe nowadays incidence of obesity is increasing as in children population, same in the adult one. Is a worldwide chronic disease and there should be take into account many aspects they are influencing the prevalence also with consideration of non-nutritive origin.Promising approaches such as whole exome and eventually whole genome sequencing, in addition to studies exploring short and long-range interactions between genes leading to obesity have the potential to guide to an exhaustive map of obesity predisposing genes in the near future. Gene identification efforts using the genetic studies have provided a more broad aspect to understand the biological mechanisms involved in the development of obesity and this information can be important not only for scientists and clinicians but for a general population too (Srivastava A., Srivastava N., Mittal, 2015).Zhang et al. (2010) confirmed the association of common variants of FTO gene with ''body fatness'' measures in an isolated island population. They also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with ''body fatness ''. Hinney et al. (2007) found that variation in FTO strongly contributes to early onset obesity.Some from the single nucleotide polymorphisms (SNP) in the FTO gene are showing 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, but Zimmermann et al. (2014) did not found that FTO SNP is associated with allcause mortality independently of the adiposity phenotypes in comparing with p...

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contrasting

confidence: 36%

Effect of FTO rs1121980 to Body Mass Index

Candráková

Trakovická

Candrák

et al. 2016

Acta fytotechn zootechn

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“…Several meta-analyses have addressed the association between FTO SNP and risk of diabetes, [ 36 ] hypertension, [ 37 ] cardiovascular disease, [ 38 ] polycystic ovary syndrome [ 39 ] and mortality [ 40 ]. Most of these meta-analyses supported FTO SNP was associated with health outcomes independently of adiposity.…”

Section: Discussionmentioning

confidence: 99%

“…Most of these meta-analyses supported FTO SNP was associated with health outcomes independently of adiposity. A meta-analysis of data from 169,551 Caucasian adults showed that the hazards ratio (HR) for the A minor allele of the FTO rs9939609 SNP was 1.02 (1.00–1.04, P =0.097), but the association disappeared after adjustment for BMI (HR=1.00; 0.98–1.03, P =0.662) [ 40 ]. These results suggested that FTO SNP risk allele increases risk of mortality directly through adiposity pathway.…”

Section: Discussionmentioning

confidence: 99%

Is FTO gene variant related to cancer risk independently of adiposity? An updated meta-analysis of 129,467 cases and 290,633 controls

Kang

Liu

2017

Oncotarget

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Previous studies have examined the association between the fat mass and obesity-associated (FTO) gene variant and risk of cancer in diverse populations. However, the results have been inconsistent. PubMed and Embase databases were searched for the eligible publications in English language by July, 2016. The associations of FTO variants with cancer risk were estimated by calculating the pooled odds ratios and 95% confidence intervals by meta-analyses. A total of 27 publications (129,467 cancer cases and 290,633 normal controls) were included in our meta-analysis. Overall, FTO rs9939609 variant (or its proxy) was not associated with cancer risk without adjustment for body mass index, as well as additional adjustment for body mss index. However, FTO rs9939609 variant was associated with some types of cancer in the subgroup analysis. In addition, overall, there was no significant association between FTO rs1477196 variant and cancer risk regardless of adjustment for body mass index. However, FTO rs11075995 variant risk allele was associated with breast cancer risk without adjustment for body mass index, but the association disappeared with further adjustment for body mass index. This study overall does not support that the FTO variant is associated with cancer risk independently of the adiposity.

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“…First, we constrained the differential death rate, which translates mathematically to

d_{a a} = d_{A a} = d_{A A} = μ

(and this is justified by an epidemiological study ). We set the death rate equal to the birth rate, in a method similar to that of a previous analysis .…”

Section: Methodsmentioning

confidence: 99%

A Mathematical Model for Predicting Obesity Transmission with Both Genetic and Nongenetic Heredity

Ejima

Thomas

Allison

2018

Obesity

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ObjectiveObesity is transmissible across generations through both genetic and nongenetic routes, but distinguishing between these factors is challenging. We aimed to quantitatively study the contribution of these genetic and nongenetic effects to assess their influence on obesity prevalence.MethodsWe proposed a mathematical model that incorporated both genetic and nongenetic effects of obesity. Model parameters were estimated by using observational data. Model simulations were used to assess the sensitivity of model parameters. To strengthen our approach, we also performed the parameter estimation and simulation using data from the UK.ResultsIndividuals homozygous for a ‘hypothetical obesogenic gene’ are suggested to be more susceptible to both social contagious risk and spontaneous weight gain risk. The model predicted that obesity prevalence reaches 41.03% (39.28, 44.31) and 26.77% (25.62, 28.06) at 2030 in the US and UK, respectively. The social contagious risk factor had a greater overall impact on the distribution of the population with obesity than did spontaneous weight gain risk or mother-to-child obesity transmission risk.ConclusionsAlthough the proposed “first approximation” model captured the complex interactions between the genetic and nongenetic effects on obesity, this framework remains incomplete. Future work should incorporate other key features driving the obesity epidemic.

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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

Cited by 9 publications

References 60 publications

Effect of FTO rs1121980 to Body Mass Index

Effect of FTO rs1121980 to Body Mass Index

Is FTO gene variant related to cancer risk independently of adiposity? An updated meta-analysis of 129,467 cases and 290,633 controls

A Mathematical Model for Predicting Obesity Transmission with Both Genetic and Nongenetic Heredity

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